Skip to main content
SpringerLink
Log in

Significance of Protein Kinase A in Cancer

  • Chapter
Apoptosis, Cell Signaling, and Human Diseases

Summary

The system of cyclic nucleotides is one of the regulatory cascades whose initial step begins at the level of the external signal perception and whose final step is completed by phosphorylation of a number of substrate proteins mediating the diverse functional responses of the cell. The study of cyclic adenosine monophosphate (cAMP) has indicated a dual effect for this nucleotide on proliferation and differentiation processes. Elevation of intracellular cAMP in normal and transformed cells can lead to the initiation of cell proliferation, or is accompanied by corresponding morphological changes and the induction of differentiation. The main target of cAMP action in the cell is cAMP-dependent protein kinase, which may exist as two different isozymes, designated as type I (PKA-I) and type II (PKA-II). These two isoforms are essentially distinct in their physicochemical properties. Such evident differences of the protein kinases, both under the control of cAMP, indicate that they act at different stages of cell life. The relative ratio of PKA-I and PKA-II varies not only throughout the cell cycle in cells of the same type, but also among tissues and during development. The data reported to date suggest that PKA-I acts as a positive growth effector, whereas PKA-II inhibits cell division. Some exceptions were described, particularly the Carney complex, which is completely attributed to mutations in the regulatory subunit of PKA-I. Thus, by modulating PKA isozymes, one can regulate the process of cell division by controlling the balance in the proliferation-differentiation system. This chapter describes a strategy for using cAMP analogs, antisense oligonucleotides, and cAMP response element (CRE) transcription factor decoy oligonucleotides to modulate the cAMP-mediated system to encounter and combat diseases, such as cancer. In connection with a newly discovered excreted form of PKA, termed extracellular PKA (ECPKA), we also discuss the possibility of using PKA as a tool in the diagnosis of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Sutherland EW, Rall TW. Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem 1958;232:1077–1092.

    PubMed  CAS  Google Scholar 

  2. Walsh DA, Perkins JP, Krebs EG. An adenosine 3′,5′-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem 1968;243:3763–3765.

    PubMed  CAS  Google Scholar 

  3. Gill GN, Garren LD. Role of the receptor in the mechanism of action of adenosine 3′:5′-cyclic monophosphate. Proc Natl Acad Sci USA 1971;68:786–790.

    Article  PubMed  CAS  Google Scholar 

  4. Kuo JF, Greengard P. Cyclic nucleotide-dependent protein kinases IV. Widespread occurrence of adenosine 3′:5′-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom. Proc Natl Acad Sci USA 1969;64:1349–1355.

    Article  PubMed  CAS  Google Scholar 

  5. Beebe SJ, Corbin JD. Cyclic nucleotide-dependent protein kinases. In: Krebs EG, Boyer PD, eds. The Enzymes: Control by Phosphorylation. Orlando and London. Academic Press, New York, 1986:43–111.

    Google Scholar 

  6. DØskeland SO, Maronde E, Gjertsen BT. The genetic subtypes of cAMP-dependent protein kinase-functionally different or redundant? Biochim Biophys Acta 1993;1178(3): 249–258.

    Article  PubMed  Google Scholar 

  7. Reimann EM, Walsh DA, Krebs EG. Purification and properties of rabbit skeletal muscle adenosine 3′:5′-monophosphate-dependent protein kinases. J Biol Chem 1971;246:1986–1995.

    PubMed  CAS  Google Scholar 

  8. Corbin JD, Keely SL, Park CR. The distribution and dissociation of cyclic adenosine 3′,5′-monophosphate-dependent protein kinases in adipose, cardiac, and other tissues. J Biol Chem 1975;250:218–225.

    PubMed  CAS  Google Scholar 

  9. Lee DC, Carmichael DF, Krebs EG, McKnight GS. Isolation of a cDNA clone for the type I regulatory subunit of bovine cAMP-dependent protein kinase. Proc Natl Acad Sci USA 1983;80:3608–3612.

    Article  PubMed  CAS  Google Scholar 

  10. Sandberg M, Tasken K, Oyen O, Hansson V, Jahnsen T. Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis. Biochem Biophys Res Commun 1987;149:939–945.

    Article  PubMed  CAS  Google Scholar 

  11. Clegg CH, Cadd GG, McKnight GS. Genetic characterization of a brain-specific form of the type I regulatory subunit of cAMP-dependent protein kinase. Proc Natl Acad Sci USA 1988;85:3703–3707.

    Article  PubMed  CAS  Google Scholar 

  12. Solberg R, Tasken K, Keiserud A, Jahnsen T. Molecular cloning, cDNA structure and tissue-specific expression of the human regulatory subunit RI beta of cAMP-dependent protein kinases. Biochem Biophys Res Commun 1991;176:166–172.

    Article  PubMed  CAS  Google Scholar 

  13. Scott JD, Glaccum MB, Zoller MJ, Uhler MD, Helfman DM, McKnight GS, et al. The molecular cloning of a type II regulatory subunit of the cAMP-dependent protein kinase from rat skeletal muscle and mouse brain. Proc Natl Acad Sci USA 1987;84:5192–5196.

    Article  PubMed  CAS  Google Scholar 

  14. Øyen O, Myklebust F, Scott JD, Hansson V, Jahnsen T. Human testis cDNA for the regulatory subunit RII alpha of cAMP-dependent protein kinase encodes an alternate aminoterminal region. FEBS Lett 1989;246:57–64.

    Article  PubMed  Google Scholar 

  15. Jahnsen T, Hedin L, Kidd VJ, Beattie WG, Lohmann SM, Walter U, et al. Molecular cloning, cDNA structure, and regulation of the regulatory subunit of type II cAMP-dependent protein kinase from rat ovarian granulosa cells. J Biol Chem 1986;261:12,352–12,361.

    PubMed  CAS  Google Scholar 

  16. Levy FO, Oyen O, Sandberg M, Tasken K, Eskild W, Hansson V, et al. Molecular cloning, complementary deoxyribonucleic acid structure and predicted full-length amino acid sequence of the hormone-inducible regulatory subunit of 3′,5′-cyclic adenosine monophosphate-dependent protein kinase from human testis. Mol Endocrinol 1988;2: 1364–1373.

    PubMed  CAS  Google Scholar 

  17. Uhler MD, Carmichael DF, Lee DC, Chrivia JC, Krebs EG, McKnight GS. Isolation of cDNA clones coding for the catalytic subunit of mouse cAMP-dependent protein kinase. Proc Natl Acad Sci USA 1986;83:1300–1304.

    Article  PubMed  CAS  Google Scholar 

  18. Uhler MD, Chrivia JC, McKnight GS. Evidence for a second isoform of the catalytic subunit of cAMP-dependent protein kinase. J Biol Chem 1986;261:15,360–15,363.

    PubMed  CAS  Google Scholar 

  19. Showers MO, Maurer RA. A cloned bovine cDNA encodes an alternate form of the catalytic subunit of cAMP-dependent protein kinase. J Biol Chem 1986;261:16,288–16,291.

    PubMed  CAS  Google Scholar 

  20. Beebe SJ, Oyen O, Sandberg M, Froysa A, Hansson V, Jahnsen T. Molecular cloning of a unique tissue-specific protein kinase (C-gamma) from human testis-representing a third isoform for the catalytic subunit of the cAMP-dependent protein kinase. Mol Endocrinol 1990;4:465–475.

    PubMed  CAS  Google Scholar 

  21. Ulmasov KhA, Nesterova MV, Severin ES. cAMP-dependent protein kinase from pig brain: subunit structure, mechanism of autophosphorylation and dissociation into subunits under the action of cAMP. Biochemistry (N.Y.) 1980;45:639–647.

    Google Scholar 

  22. Corbin JD, Keely SL, Soderling TR, Park CR. Hormonal regulation of adenosine 3′,5′-monophosphate-dependent protein kinase. Adv Cyclic Nucleotide Res 1975;5:265–279.

    PubMed  CAS  Google Scholar 

  23. Hofman F, Beavo JA, Bechtel PJ, Krebs EG. Comparison of adenosine 3′,5′-monophosphate-dependent protein kinase from rabbit skeletal and bovine heart muscle. J Biol Chem 1975;250:7795–7801.

    Google Scholar 

  24. Rangel-Aldao R, Rosen OM. Mechanism of self-phosphorylation of adenosine 3′:5′-monophosphate-depedent protein kinase from bovine cardiac muscle. J Biol Chem 1976;251:3375–3380.

    PubMed  CAS  Google Scholar 

  25. Dostmann WR, Taylor SS, Genieser HG, Jastorff B, Doskeland SO, Ogreid D. Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3′,5′-cyclic phosphorothioates. J Biol Chem 1990;265:10,484–10,491.

    PubMed  CAS  Google Scholar 

  26. Hofman F. Apparent constants for the interaction of regulatory and catalytic subunit of cAMP-dependent protein kinase I and II. J Biol Chem 1980;255:1559–1564.

    Google Scholar 

  27. Otten AD, McKnight GS. Overexpression of the type II regulatory subunit of the cAMPdependent protein kinase eliminates the type I holoenzyme in mouse cells. J Biol Chem 1989;264:20,255–20,260.

    PubMed  CAS  Google Scholar 

  28. Amieux PS, Cummings DE, Motamed K, Brandon EP, Wailes LA, Le K, et al. Compensatory regulation of RIalpha protein levels in protein kinase A mutant mice. J Biol Chem 1997;272:3993–3998.

    Article  PubMed  CAS  Google Scholar 

  29. Tasken K, Skalhegg BS, Solberg R, Andersson KB, Taylor SS, Lea T, et al. Novel isozymes of cAMP-dependent protein kinase exist in human cells due to formation of RI alpha-RI beta heterodimeric complexes. J Biol Chem 1993;268:21,276–21,283.

    PubMed  CAS  Google Scholar 

  30. Sugden PH, Corbin JD. Adenosine 3′:5′-cyclic monophosphate-binding proteins in bovine and rat tissues. Biochem J 1976;159:423–427.

    PubMed  CAS  Google Scholar 

  31. Hofmann F, Bechtel PJ, Krebs EG. Concentrations of cyclic AMP-dependent protein kinase subunits in various tissues. J Biol Chem 1977;252(4):1441–1447.

    PubMed  CAS  Google Scholar 

  32. Scott JD, McCartney S. Localization of A-kinase through anchoring proteins. Mol Endocrinol 1994;8:5–11.

    Article  PubMed  CAS  Google Scholar 

  33. Meinkoth JL, Ji Y, Taylor SS, Feramisco JR. Dynamics of the distribution of cyclic AMPdependent protein kinase in living cells. Proc Natl Acad Sci USA 1990;87:9595–9599.

    Article  PubMed  CAS  Google Scholar 

  34. Vallee RB, DiBartolomeis MJ, Theurkauf WE. A protein kinase bound to the projection portion of MAP 2 (microtubule-associated protein 2). J Cell Biol 1981;90(3):568–576.

    Article  PubMed  CAS  Google Scholar 

  35. Imaizumi-Scherrer T, Faust DM, Barradeau S, Hellio R, Weiss MC. Type I protein kinase a is localized to interphase microtubules and strongly associated with the mitotic spindle. Exp Cell Res 2001;264:250–265.

    Article  PubMed  CAS  Google Scholar 

  36. Keryer G, Skalhegg BS, Landmark BF, Hansson V, Jahnsen T, Tasken K. Differential localization of protein kinase A type II isozymes in the Golgi-centrosomal area. Exp Cell Res 1999;249:131–146.

    Article  PubMed  CAS  Google Scholar 

  37. Keryer G, Yassenko M, Labbe JC, Castro A, Lohmann SM, Evain-Brion D, et al. Mitosisspecific phosphorylation and subcellular redistribution of the RIIalpha regulatory subunit of cAMP-dependent protein kinase. J Biol Chem 1998;273:34,594–34,602.

    Article  PubMed  CAS  Google Scholar 

  38. Carlson CR, Witczak O, Vossebein L, et al. CDK1-mediated phosphorylation of the RIIalpha regulatory subunit of PKA works as a molecular switch that promotes dissociation of RIIalpha from centrosomes at mitosis. J Cell Sci 2001;114:3243–3254.

    PubMed  CAS  Google Scholar 

  39. Kondrashin AA, Nesterova MV, Cho-Chung YS. Subcellular distribution of the R-subunits of cAMP-dependent protein kinase in LS-174T human colon carcinoma cells. Biochem Mol Biol Int 1998;45:237–244.

    PubMed  CAS  Google Scholar 

  40. Kondrashin A, Nesterova M, Cho-Chung YS. Cyclic adenosine 3′:5′-monophosphatedependent protein kinase on the external surface of LS-174T human colon carcinoma cells. Biochemistry 1999;38:172–179.

    Article  PubMed  CAS  Google Scholar 

  41. Riabowol KT, Fink JS, Gilman MZ, Walsh DA, Goodman RH, Feramisco JR. The catalytic subunit of cAMP-dependent protein kinase induces expression of genes containing cAMPresponsive enhancer elements. Nature 1988;336:83–86.

    Article  PubMed  CAS  Google Scholar 

  42. Solberg R, Tasken K, Wen W, et al. Human regulatory subunit RI beta of cAMP-dependent protein kinases: expression, holoenzyme formation and microinjection into living cells. Exp Cell Res 1994;214:595–605.

    Article  PubMed  CAS  Google Scholar 

  43. Neary CL, Cho-Chung YS. Nuclear translocation of the catalytic subunit of protein kinase A induced by an antisense oligonucleotide directed against the RIalpha regulatory subunit. Oncogene 2001;20:8019–8024.

    Article  PubMed  CAS  Google Scholar 

  44. Nesterova MV, Ulmasov KHA, Abdukarimov A, Aripdzhanov AA, Severin ES. Nuclear translocation of cAMP-dependent protein kinase. Expl Cell Res 1981;132:367–373.

    Article  CAS  Google Scholar 

  45. Aprikian AG, Nesterova MV, Glukhov AI, Severin ES. Binding of a holoenzyme and cAMPdependent protein kinase subunits with cell nuclei. Biochemistry (NY)1987;52: 1118–1124.

    Google Scholar 

  46. Kapoor CL, Grantham F, Cho-Chung YS. Nucleolar accumulation of cyclic adenosine 3′:5′-monophosphate receptor proteins during regression of MCF-7 human breast tumor. Cancer Res 1984;44:3554–3560.

    PubMed  CAS  Google Scholar 

  47. Constantinescu A, Wu M, Asher O, Diamond I. cAMP-dependent protein kinase type I regulates ethanol-induced cAMP response element-mediated gene expression via activation of CREB-binding protein and inhibition of MAPK. J Biol Chem 2004;279: 43,321–43,329.

    Article  PubMed  CAS  Google Scholar 

  48. Neary CL, Nesterova M, Cho YS, Cheadle C, Becker KG, Cho-Chung YS. Protein kinase A isozyme switching: eliciting differential cAMP signaling and tumor reversion. Oncogene 2004;23:8847–8856.

    Article  PubMed  CAS  Google Scholar 

  49. Feliciello A, Giuliano P, Porcellini A, et al. The v-Ki-Ras oncogene alters cAMP nuclear signaling by regulating the location and the expression of cAMP-dependent protein kinase IIβ. J Biol Chem 1996; 271:25,350–25,359.

    Article  PubMed  CAS  Google Scholar 

  50. Haddox MK, Roeske WR, Russell DH. Independent expression of cardiac type I and II cyclic AMP-dependent protein kinase during murine embryogenesis and postnatal development. Biochim Biophys Acta 1979;585:527–534.

    PubMed  CAS  Google Scholar 

  51. Malkinson AM, Hogy L, Gharrett AJ, Gunderson TJ. Ontogenetic studies of cyclic AMPdependent protein kinase enzymes from mouse heart and other tissues. J Exp Zool 1978; 205:423–431.

    Article  PubMed  CAS  Google Scholar 

  52. Claycomb WC. Biochemical aspects of cardiac muscle differentiation. Deoxyribonucleic acid synthesis and nuclear and cytoplasmic deoxyribonucleic acid polymerase activity. J Biol Chem 1975;250:3229–3235.

    PubMed  CAS  Google Scholar 

  53. Jonassen JA, Bose K, Richards JS. Enhancement and desensitization of hormone-responsive adenylate cyclase in granulosa cells of preantral and antral ovarian follicles: effects of estradiol and follicle-stimulating hormone. Endocrinology 1982;111:74–79.

    Article  PubMed  CAS  Google Scholar 

  54. Fuller DJ, Byus CV, Russell DH. Specific regulation by steroid hormones of the amount of type I cyclic AMP-dependent protein kinase holoenzyme. Proc Natl Acad Sci USA 1978; 75:223–227.

    Article  PubMed  CAS  Google Scholar 

  55. Costa M, Gerner EW, Russell DH. Cell cycle-specific activity of type I and type II cyclic adenosine 3′:5′-monophosphate-dependent protein kinases in Chinese hamster ovary cells. J Biol Chem 1976;251(11):3313–3319.

    PubMed  CAS  Google Scholar 

  56. Byus CV, Klimpel GR, Lucas DO, Russell DH. Type I and type II cyclic AMP-dependent protein kinase as opposite effectors of lymphocyte mitogenesis. Nature 1977;268:63–64.

    Article  PubMed  CAS  Google Scholar 

  57. Kammer GM. The adenylate cyclase-cAMP-protein kinase A pathway and regulation of the immune response. Immunol Today 1988;9:222–229.

    Article  PubMed  CAS  Google Scholar 

  58. Laxminarayana D, Kammer GM. Activation of type I protein kinase A during receptormediated human T lymphocyte activation. J Immunol 1996;156:497–506.

    PubMed  CAS  Google Scholar 

  59. Skalhegg BS, Landmark BF, Doskeland SO, Hansson V, Lea T, Jahnsen T. Cyclic AMPdependent protein kinase type I mediates the inhibitory effects of 3′,5′-cyclic adenosine monophosphate on cell replication in human T lymphocytes. J Biol Chem 1992;267: 15,707–15,714.

    PubMed  CAS  Google Scholar 

  60. Tasken K, Andersson KB, Erikstein BK, Hansson V, Jahnsen T, Blomhoff HK. Regulation of growth in a neoplastic B cell line by transfected subunits of 3′,5′-cyclic adenosine monophosphate-dependent protein kinase. Endocrinology 1994;135:2109–2119.

    Article  PubMed  CAS  Google Scholar 

  61. Schwartz DA, Rubin CS. Regulation of cAMP-dependent protein kinase subunit levels in Friend erythroleukemic cells. J Biol Chem 1983;258:777–784.

    PubMed  CAS  Google Scholar 

  62. Strickland S, Smith KK, Marotti KR. Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cAMP. Cell 1980;21:347–355.

    Article  PubMed  CAS  Google Scholar 

  63. Plet A, Evain D, Anderson WB. Effect of retinoic acid treatment of F9 embryonal carcinoma cells on the activity and distribution of cyclic AMP-dependent protein kinase. J Biol Chem 1982;257:889–893.

    PubMed  CAS  Google Scholar 

  64. Ng KW, Livesey SA, Larkins RG, Martin TJ. Calcitonin effects on growth and on selective activation of type II isoenzyme of cyclic adenosine 3′:5′-monophosphate-dependent protein kinase in T 47D human breast cancer cells. Cancer Res 1983;43:794–800.

    PubMed  CAS  Google Scholar 

  65. Cho-Chung YS. Hypothesis: cyclic AMP and its receptor protein in tumor growth regulation in vivo. J Cyclic Nucl Res 1980;6:163–177.

    CAS  Google Scholar 

  66. Russell DH. Type I cyclic AMP-dependent protein kinase as a positive effector of growth. Adv Cycl Nucl Res 1978;9:493–506.

    CAS  Google Scholar 

  67. Katsaros D, Tortora G, Tagliaferri P, et al. Site-selective cyclic AMP analogs provide a new approach in the control of cancer cell growth. FEBS Lett 1987;223:97–103

    Article  PubMed  CAS  Google Scholar 

  68. Cho-Chung YS, Clair T, Tagliaferri P, et al. Site-selective cyclic AMP analogs as new biological tools in growth control, differentiation and proto-oncogene regulation. Cancer Inv 1989;7:161–177.

    CAS  Google Scholar 

  69. Eppenberger U, Briedermann K, Handshin JC, et al. Cyclic AMP-dependent protein kinase type I and type II and cyclic AMP binding in human mammary tumours. Adv Cyclic Nucleotide Res 1980;12:123–128.

    PubMed  CAS  Google Scholar 

  70. Katsaros D, Ally S, Cho-Chung YS. Site-selective cyclic AMP analogues are antagonistic to estrogen stimulation of growth and proto-oncogene expression in human breast-cancer cells. Int J Cancer 1988;41:863–867.

    Article  PubMed  CAS  Google Scholar 

  71. Miller WR. Regulatory subunits of PKA and breast cancer. Ann NY Acad Sci 2002;968: 37–48.

    PubMed  CAS  Google Scholar 

  72. Fossberg TM, Doskeland SO, Ueland PM. Protein kinases in human renal cell carcinoma and renal cortex. A comparison of isozyme distribution and of responsiveness to adenosine 3′:5′-cyclic monophosphate. Arch Biochem Biophys 1978;189:372–381.

    Article  CAS  Google Scholar 

  73. Nakajima F, Imashuku S, Wilimas J, Champion JE, Green AA. Distribution and properties of type I and type II binding proteins in the Wilms’ tumors. Cancer Res 1984;44: 5182–5187.

    PubMed  CAS  Google Scholar 

  74. Bradbury AW, Miller WR, Clair T, Yokozaki H, Cho-Chung YS. Overexpressed type I regulatory subunit (RI) of cAMP-dependent protein kinase (PKA) as tumor marker in colorectal cancer. Proc Am Assoc Cancer Res 1990;31:172.

    Google Scholar 

  75. Sand G, Jortay A, Pochet R, Dumont JE. Adenylate cyclase and protein phosphokinase activities in human thyroid. Comparison of normal glands, hyperfunctional nodules and carcinomas 1976;12:447–453.

    CAS  Google Scholar 

  76. Trabucchi M, Canal N, Frattola L. Cyclic nucleotides in human cerebral tumors: role of the protein kinase system. Adv Cyclic Nucleotide Protein Phosphorylation Res 1984;17: 671–676.

    PubMed  CAS  Google Scholar 

  77. Pena JM, Itarte E, Domingo A, Cusso R. Cyclic adenosine3′:5′-monophosphate-dependent and-independent protein kinases in human leukemic cells. Cancer Res 1983;43:1172–1175.

    PubMed  CAS  Google Scholar 

  78. Weber W, Schwoch G, Wielckens K, Gartemann A, Hilz H. cAMP receptor proteins and protein kinases in human lymphocytes: fundamental alterations in chronic lymphocytic leukemia cells. Eur J Biochem 1981;120:585–592.

    Article  PubMed  CAS  Google Scholar 

  79. Cho-Chung YS, Clair T, Shepheard C. Anticarcinogenic effect of N6,O2-dibutyryl cyclic adenosine 3′,5′-monophosphate on 7,12-dimethylbenz(α) anthracene mammary tumor induction in the rat and its relationship to cyclic adenosine 3′,5′-monophosphate metabolism and protein kinase. Cancer Res 1983;43:2736–2740.

    PubMed  CAS  Google Scholar 

  80. Yasui W, Tahara E. Effect of gastrin on gastric mucosal cyclic adenosine 3′,5′-monophosphate-dependent protein kinase activity in rat stomach carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine. Cancer Res 1985;45:4763–4767.

    PubMed  CAS  Google Scholar 

  81. Butley MS, Stoner GD, Beer DG, Beer DS, Mason RJ, Malkinson AM. Changes in cyclic adenosine 3′:5′-monophosphate-dependent protein kinases during the progression of urethan-induced mouse lung tumors. Cancer Res 1985;45:3677–3685.

    PubMed  CAS  Google Scholar 

  82. Lange-Carter CA, Fossli T, Jahnsen T, Malkinson AM. Decreased expression of the type I isozyme of cAMP-dependent protein kinase in tumor cell lines of lung epithelial origin. J Biol Chem 1990;265:7814–7818.

    PubMed  CAS  Google Scholar 

  83. Wehner JM, Malkinson AM, Wiser MF, Sheppard JR. Cyclic AMP-dependent protein kinases from Balb 3T3 cells and other 3T3 derived lines. J Cell Physiol 1981;108:175–184.

    Article  PubMed  CAS  Google Scholar 

  84. Ledinko N, Chan IJ. Increase in type I cyclic adenosine 3′:5′-monophosphate-dependent protein kinase activity and specific accumulation of type I regulatory subunits in adenovirus type 12-transformed cells. Cancer Res 1984;44:2622–2627.

    PubMed  CAS  Google Scholar 

  85. Tagliaferri P, Katsaros D, Clair T, Neckers L, Robins RK, Cho-Chung YS. Reverse transformation of Harvey murine sarcoma virus-transformed NIH/3T3 cells by site-selective cyclic AMP analogs. J Biol Chem 1988;263:409–416.

    PubMed  CAS  Google Scholar 

  86. Tortora G, Ciardiello F, Ally S, Clair T, Salomon DS, Cho-Chung YS. Site-selective 8-chloroadenosine 3′,5′-cyclic monophosphate inhibits transformation and transforming growth factor alpha production in Ki-ras-transformed rat fibroblasts. FEBS Lett 1989;242: 363–367.

    Article  PubMed  CAS  Google Scholar 

  87. Ciardiello F, Tortora G, Kim N, et al. 8-chloro-cAMP inhibits transforming growth factor α transformation of mammary epithelial cells by restoration of the normal mRNA patterns for cAMP-dependent protein kinase regulatory subunit isoforms which show disruption upon transformation. J Biol Chem 1990;265:1016–1020.

    PubMed  CAS  Google Scholar 

  88. Ally S, Tortora G, Clair T, et al. Selective modulation of protein kinase isozymes by the site-selective analog 8-chloroadenosine 3′,5′-cyclic monophosphate provides a biological means for control of human colon cancer cell growth. Proc Natl Acad Sci USA 1988;85: 6319–6322.

    Article  PubMed  CAS  Google Scholar 

  89. Ally S, Clair T, Katsaros D, et al. Inhibition of growth and modulation of gene expression in human lung carcinoma in athymic mice by site-selective 8-Cl-cyclic adenosine monophosphate. Cancer Res 1989;49:5650–5655.

    PubMed  CAS  Google Scholar 

  90. Tortora G, Yokozaki H, Pepe S, Clair T, Cho-Chung YS. Differentiation of HL-60 leukemia cells by type I regulatory subunit antisense oligodeoxynucleotide of cAMP-dependent protein kinase. Proc Natl Acad Sci USA 1991;88:2011–2015.

    Article  PubMed  CAS  Google Scholar 

  91. Yokozaki H, Budillon A, Tortora G, et al. An antisense oligodeoxynucleotide that depletes RIα subunit of cyclic AMP-dependent protein kinase induces growth inhibition in human cancer cells. Cancer Res 1993;53:868–872.

    PubMed  CAS  Google Scholar 

  92. Tortora G, Cho-Chung YS. Type II regulatory subunit of protein kinase restores cAMPdependent transcription in a cAMP-unresponsive cell line. J Biol Chem 1990;265: 18,067–18,070.

    PubMed  CAS  Google Scholar 

  93. Gupte RS, Weng Y, Liu L, Lee MY. The Second Subunit of the Replication Factor C complex (RFC40) and the Regulatory Subunit (RIalpha) of Protein Kinase A Form a Protein Complex Promoting Cell Survival. Cell Cycle 2005;4:323–329.

    PubMed  CAS  Google Scholar 

  94. Levin DS, Vijayakumar S, Liu X, Bermudez VP, Hurwitz J, Tomkinson AE. A conserved interaction between the replicative clamp loader and DNA ligase in eukaryotes: implications for Okazaki fragment joining. J Biol Chem 2004;279:55,196–55,201.

    Article  PubMed  CAS  Google Scholar 

  95. Parrilla-Castellar ER, Arlander SJ, Karnitz L. Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex. DNA Repair (Amst) 2004;3:1009–1014.

    Article  CAS  Google Scholar 

  96. Durgerian S, Taylor SS. The consequences of introducing an autophosphorylation site into the type I regulatory subunit of cAMP-dependent protein kinase. J Biol Chem 1989;264: 9807–9813.

    PubMed  CAS  Google Scholar 

  97. Kuret J, Johnson KE, Nicolette C, Zoller MJ. Mutagenesis of the regulatory subunit of yeast cAMP-dependent protein kinase: Isolation of site-directed mutants with altered binding affinity for catalytic subunit. J Biol Chem 1988;263:9149–9154.

    PubMed  CAS  Google Scholar 

  98. Nesterova MV, Yokozaki H, McDuffie L, Cho-Chung YS. Overexpression of RIIβ regulatory subunit of protein kinase A in human colon carcinoma cell induces growth arrest and phenotypic changes that are abolished by site-directed mutation of RIIβ. Eur J Biochem 1996;235:486–494.

    Article  PubMed  CAS  Google Scholar 

  99. Lee GR, Kim SN, Noguchi K, Park SD, Hong SH, Cho-Chung YS. Ala99ser mutation in RI alpha regulatory subunit of protein kinase A causes reduced kinase activation by cAMP and arrest of hormone-dependent breast cancer cell growth. Mol Cell Biochem 1999;195:77–86.

    Article  PubMed  CAS  Google Scholar 

  100. Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000; 26: 89–92.

    Article  PubMed  CAS  Google Scholar 

  101. Bossis I, Voutetakis A, Bei T, Sandrini F, Griffin KJ, Stratakis CA. Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer 2004;11: 265–280.

    Article  PubMed  CAS  Google Scholar 

  102. Griffin KJ, Kirschner LS, Matyakhina L, et al. Down-regulation of regulatory subunit type 1A of protein kinase A leads to endocrine and other tumors. Cancer Res 2004;64: 8811–8815.

    Article  PubMed  CAS  Google Scholar 

  103. Griffin KJ, Kirschner LS, Matyakhina L, et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet 2004;41:923–931.

    Article  PubMed  CAS  Google Scholar 

  104. Lania AG, Mantovani G, Ferrero S, et al. Proliferation of transformed somatotroph cells related to low or absent expression of protein kinase a regulatory subunit 1A protein. Cancer Res 2004;64:9193–9198.

    Article  PubMed  CAS  Google Scholar 

  105. Burk RR. Reduced adenyl cyclase activity in a polyomavirus transformed cell line. Nature 1968;219:1272–1275.

    Article  Google Scholar 

  106. Johnson GS, Friedman RM, Pastan I. Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3′,5′-cycle monophosphate and its derivatives. Proc Natl Acad Sci USA 1971;68:425–429.

    Article  PubMed  CAS  Google Scholar 

  107. Cho-Chung YS, Gullino PM. In vivo inhibition of growth of two hormone-dependent mammary tumors by dibutyryl cyclic AMP. Science 1974;183:87–88.

    Article  PubMed  CAS  Google Scholar 

  108. DØskeland SO. Evidence that rabbit muscle protein kinase has two kinetically distinct binding sites for adenosine 3′,5′-cyclic monophosphate. Biochem Biophys Res Commun 1978;83:542–549.

    Article  PubMed  Google Scholar 

  109. Rannels SR, Corbin JD. Two different intrachain cAMP binding sites of cAMP-dependent protein kinases. J Biol Chem 1980;255:7085–7088.

    PubMed  CAS  Google Scholar 

  110. Cho-Chung YS. Commentary: site-selective 8-chloro-cyclic adenosine 3′,5′-monophosphate as a biologic modulator of cancer: restoration of normal control mechanisms. J Natl Cancer Inst 1989;81:982–987.

    Article  PubMed  CAS  Google Scholar 

  111. Ogreid D, Ekanger R, Suva RH, et al. Activation of protein kinase isozymes by cyclic nucleotide analogs used singly or in combination. Principles for optimizing the isozyme specificity of analog combinations. Eur J Biochem 1985;150:219–227.

    Article  PubMed  CAS  Google Scholar 

  112. Cho-Chung YS. Role of cyclic AMP receptor proteins in growth, differentiation, and suppression of malignancy: new approaches to therapy. Cancer Res 1990;50:7093–7100.

    PubMed  CAS  Google Scholar 

  113. Halgren RG, Traynor AE, Pillay S, et al. 8Cl-cAMP cytotoxicity in both steroid sensitive and insensitive multiple myeloma cell lines is mediated by 8Cl-adenosine. Blood 1998; 92:2893–2898.

    PubMed  CAS  Google Scholar 

  114. Tagliaferri P, Katsaros D, Clair T, et al. Synergistic inhibition of growth of breast and colon human cancer cell lines by site-selective cyclic AMP analogues. Cancer Res 1988;48: 1642–1650.

    PubMed  CAS  Google Scholar 

  115. Koontz JW, Wicks WD. Cytotoxic effects of two novel 8-substituted cyclic nucleotide derivaties in cultured rat hepatoma cells. Mol Pharmacol 1980;18:65–71.

    PubMed  CAS  Google Scholar 

  116. Koontz JW, Wicks WD. Comparison of the effects of 6-thio-and 6-methylthiopurine ribonucleoside cyclic monophosphates with their corresponding nucleosides on the growth of rat hepatoma cells. Cancer Res 1977;37:651–657.

    PubMed  CAS  Google Scholar 

  117. Cho-Chung YS, Budillon A, Nesterova M, Tortora G, Kondrashin A, Lee GR. Development of 8-Cl-cAMP as differentiation agent. In:Challenges of Modern Medicine, Serono Symposium Publication series/Diffrentiation Therapy 1995;10:183–198.

    Google Scholar 

  118. Tortora G, Clair T, Katsaros D, et al. Induction of megakaryocytic differentiation and modulation of protein kinase gene expression by site-selective cAMP analogs in K-562 human leukemic cells. Proc Natl Acad Sci USA 1989;86:2849–2852.

    Article  PubMed  CAS  Google Scholar 

  119. Srivastava RK, Srivastava AR, Cho-Chung YS, Longo DL. Synergistic effects of retinoic acid and 8-chloro-adenosine 3′,5′-cyclic monophosphate on the regulation of retinoic acid receptor beta and apoptosis: involvement of mitochondria. Clin Cancer Res 1999;5: 1892–1904.

    PubMed  CAS  Google Scholar 

  120. Kim SN, Kim SG, Park JH, et al. Dual anticancer activity of 8-Cl-cAMP: inhibition of cell proliferation and induction of apoptotic cell death. Biochem Biophys Res Commun 2000; 273:404–410.

    Article  PubMed  CAS  Google Scholar 

  121. Rohlff CT, Clair T, Cho-Chung YS. 8-Cl-cAMP induces trancation and down-regulation of the RIα subunit and up-regulation of the RIIβ subunit of cAMP-dependent protein kinase leading to type II holoenzyme-dependent growth inhibition and differentiation of HL-60 leukemia cells. J Biol Chem 1993;268:5774–5782.

    PubMed  CAS  Google Scholar 

  122. Harada H, Becknell B, Wilm M, et al. Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. Mol Cell 1999;3:413–422.

    Article  PubMed  CAS  Google Scholar 

  123. Pinto A, Aldinucci D, Gattel V, et al. Inhibition of the self-renewal capacity of blast progenitors from acute myeloblastic leukemia patients by site-selective 8-chloroadenosine 3′,5′-cyclic monophosphate. Proc Natl Acad Sci USA 1992;89:8884–8888.

    Article  PubMed  CAS  Google Scholar 

  124. Tortora G, Ciardiello F, Pepe S, et al. Phase I clinical study with 8-chloro-cAMP and evaluation of immunological effects in cancer patients. Clin Cancer Res 1995;4:377–384.

    Google Scholar 

  125. Weissinger EM, Oettrich K, Evans C, et al. Activation of protein kinase A (PKA by 8-ClcAMP as a novel approach for antileukaemic therapy. Br J Cancer 2004;91:186–192.

    Article  PubMed  CAS  Google Scholar 

  126. Tortora G, Pepe S, Yokozaki H, Clair T, Rohlff C, Cho-Chung YS. A RIa subunit antisense oligonucleotide of cAMP-dependent protein kinase inhibits proliferation of human HL-60 promyelocytic lekemia. Proc Am Acssoc Cancer Res 1990;31:38.

    Google Scholar 

  127. Tortora G, Clair T, Cho-Chung YS. An antisense oligodeoxynucleotide targeted against the type RII beta regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects. Proc Natl Acad Sci USA 1990;87:705–708.

    Article  PubMed  CAS  Google Scholar 

  128. Schwartz DA, Rubin CS. Identification and differential expression of two forms of regulatory subunits (RII) of cAMP-dependent protein kinase II in Friend urythroleukemic cells. J Biol Chem 1985;260:6063–6296.

    Google Scholar 

  129. Nesterova M, Cho-Chung YS. A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth. Nat Med 1995;1:528–633.

    Article  PubMed  CAS  Google Scholar 

  130. Nesterova M, Noguchi K, Park YG, Lee YN, Cho-Chung YS. Compensatory stabilization of RIIβ protein, cell cycle deregulation, and growth arrest in colon and prostate carcinoma cells by antisense-directed down-regulation of protein kinase A RIα protein. Clin Cancer Res 2000;6:3434–3441.

    PubMed  CAS  Google Scholar 

  131. Agrawal S, Jiang Z, Zhao Q, et al. Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in vivo studies. Proc Natl Acad Sci USA 1997;94: 2620–2625.

    Article  PubMed  CAS  Google Scholar 

  132. Chen HX, Marshall JL, Ness E, Martin RR, Dvorchik B, Rizvi N, et al. A safety and pharmacokinetic study of a mixed-backbone oligonucleotide (GEM 231) targeting the type I protein kinase A by two-hour infusions in patients with refractory solid tumors. Clin Cancer Res 2000;6:1259–1266.

    PubMed  CAS  Google Scholar 

  133. Agrawal S, Zhao Q. Mixed backbone oligonucleotides: improvement in oligonucleotideinduced toxicity in vivo. Antisense Nucleic Acid Drug Dev 1998;8:135–139.

    PubMed  CAS  Google Scholar 

  134. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995;374(6522):546–549.

    Article  PubMed  CAS  Google Scholar 

  135. Metelev V, Liszlewicz J, Agrawal S. Study of antisense oligonucleotide phosphorothioates containing segments of oligodeoxynucleotides and 2′-O-methyloligoribonucleotides. Bioorg Med Chem Lett 1994;4:2929–2934.

    Article  CAS  Google Scholar 

  136. Monia BP, Lesnik EA, Gonzalez C, Lima WF, McGee D, Guinosso CJ, et al. Evaluation of 2′-modified oligonucleotides containing 2′-deoxygaps as antisense inhibitors of gene expression. J Biol Chem 1993;268:14,514–14,522.

    PubMed  CAS  Google Scholar 

  137. Shibahara S, Mukai S, Morisawa H, Nakashima H, Kobayashi S, Yamamoto N. Inhibition of human immunodeficiency virus (HIV-1) replication by synthetic oligo-RNA derivatives. Nucleic Acids Res 1989;17:239–252.

    Article  PubMed  CAS  Google Scholar 

  138. Tortora G, Ciardiello F. Protein kinase A as target for novel integrated strategies of cancer therapy. Ann NY Acad Sci 2002;968:139–147.

    Article  PubMed  CAS  Google Scholar 

  139. Ciardiello F, Pepe S, Bianco C, et al. Down-regulation of RIα subunit of cAMP-dependent protein kinase induces growth inhibition of human mammary epithelial cells transformed by c-Ha-ras and c-erbB-2 proto-oncogenes. Int J Cancer 1993;53:438–443.

    Article  PubMed  CAS  Google Scholar 

  140. Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annu Rev Med 2002; 53: 35–57.

    Article  PubMed  CAS  Google Scholar 

  141. Srivastava RK, Srivastava AR, Korsmeyer SJ, Nesterova M, Cho-Chung YS, Longo DL. Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase. Mol Cell Biol 1998;18:3509–3517.

    PubMed  CAS  Google Scholar 

  142. Alper O, Hacker NF, Cho-Chung YS. Protein kinase A-Ialpha subunit-directed antisense inhibition of ovarian cancer cell growth: crosstalk with tyrosine kinase signaling pathway. Oncogene 1999;18:4999–5004.

    Article  PubMed  CAS  Google Scholar 

  143. Cho YS, Kim M-K, Cheadle C, Neary C, Becker KG, Cho-Chung YS. Antisense DNAs as multisite genomic modulators identified by DNA microarray. Proc Natl Acad Sci USA 2001;98:9819–9823.

    Article  PubMed  CAS  Google Scholar 

  144. Tortora G, Caputo R, Damiano V, et al. Synergistic inhibition of human cancer cell growth by cytotoxic drugs and mixed backbone antisense oligonucleotide targeting protein kinase A. Proc Natl Acad Sci USA 1997;94:12,586–12,591.

    Article  PubMed  CAS  Google Scholar 

  145. Wang H, Cai Q, Zeng X, Yu D, Agrawal S, Zhang R. Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIalpha subunit of protein kinase A after oral administration. Proc Natl Acad Sci USA 1999;96:13,989–13,994.

    Article  PubMed  CAS  Google Scholar 

  146. Tortora G, Bianco R, Damiano V, et al. Oral antisense that targets protein kinase A cooperates with taxol and inhibits tumor growth, angiogenesis, and growth factor production. Clin Cancer Res 2000;6:2506–2512.

    PubMed  CAS  Google Scholar 

  147. Wang H, Hang J, Shi Z, et al. Antisense oligonucleotide targeted to RIalpha subunit of cAMP-dependent protein kinase (GEM231) enhances therapeutic effectiveness of cancer chemotherapeutic agent irinotecan in nude mice bearing human cancer xenografts: in vivo synergistic activity, pharmacokinetics and host toxicity. Int J Oncol 2002;21:73–80.

    PubMed  CAS  Google Scholar 

  148. Tortora G, Damiano V, Bianco C, et al. The RIα subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor. Oncogene 1997;14:923–928.

    Article  PubMed  CAS  Google Scholar 

  149. Tortora G, Ciardiello F. Targeting of epidermal growth factor receptor and protein kinase A: molecular basis and therapeutic applications. Ann Oncol 2000;11:777–783.

    Article  PubMed  CAS  Google Scholar 

  150. Yang WL, Iacono L, Tang WM, Chin KV. Novel function of the regulatory subunit of protein kinase A: regulation of cytochrome c oxidase activity and cytochrome c release. Biochemistry 1998;37:14,175–14,180

    Article  PubMed  CAS  Google Scholar 

  151. Srivastava RK, Srivastava AR, Park YG, Agrawal S, Cho-Chung YS. Antisense depletion of RIalpha subunit of protein kinase A induces apoptosis and growth arrest in human breast cancer cells. Breast Cancer Res Treat 1998;49:97–107.

    Article  PubMed  CAS  Google Scholar 

  152. Cho YS, Kim MK, Tan L, Srivastava R, Agrawal S, Cho-Chung YS. Protein kinase A RIα antisense inhibition of PC3M prostate cancer cell growth: Bcl-2 hyperphosphorylation, Bax up-regulation, and Bad-hypophosphorylation. Clin Cancer Res 2002;8:607–614.

    PubMed  CAS  Google Scholar 

  153. Tortora G, Caputo R, Damiano V, et al. Combined blockade of protein kinase A and bcl-2 by antisense strategy induces apoptosis and inhibits tumor growth and angiogenesis. Clin Cancer Res 2001;7:2537–2544.

    PubMed  CAS  Google Scholar 

  154. Nesterova MV, Cho-Chung YS. Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz( a)anthracene-induction of mammary cancer: blockade at the initial phase of carcinogenesis. Clin Cancer Res 2004;10:4568–4577.

    Article  PubMed  CAS  Google Scholar 

  155. Mayr B, Montminy M. Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2001;2:599–609.

    Article  PubMed  CAS  Google Scholar 

  156. Conkright MD, Guzman E, Flechner L, et al. Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness. Mol Cell 2003;11:1101–1108.

    Article  PubMed  CAS  Google Scholar 

  157. Montminy MR, Bilezikjian LM. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 1987;328:175–178.

    Article  PubMed  CAS  Google Scholar 

  158. Montminy MR, Sevarino KA, Wagner JA, Mandel G, Goodman HM. Identificaiton of a cyclic-AMP-responsive element with the rat somatostatin gene. Proc Natl Acad Sci USA 1986;83:6682–6686.

    Article  PubMed  CAS  Google Scholar 

  159. Moriuchi A, Ido A, Nagata Y, et al. A CRE and the region occupied by a protein induced by growth factors contribute to up-regulation of cyclin D1 expression in hepatocytes. Biochem Biophys Res Commun 2003;300:415–421.

    Article  PubMed  CAS  Google Scholar 

  160. Droogmans L, Cludts I, Cleuter Y, Kettmann R, Burny A. Nucleotide sequence of the bovine interleukin-6 gene promoter. DNA Seq 1992;3:115–117.

    PubMed  CAS  Google Scholar 

  161. Russell DL, Doyle KM, Gonzales-Robayna I, Pipaon C, Richards JS. Egr-1 induction in rat granulosa cells by follicle-stimulating hormone and luteinizing hormone: combinatorial regulation by transcription factors cyclic adenosine 3′,5′-monophosphate regulatory element binding protein, serum response factor, sp1, and early growth response factor-1. Mol Endocrinol 2003;17:520–533.

    Article  PubMed  CAS  Google Scholar 

  162. Park YG, Nesterova M, Agrawal S, Cho-Chung YS. Dual blockade of cyclic AMP response element (CRE)-and AP-1-directed transcription by CRE transcription factor decoy oligonucleotide: Gene-specific inhibition of tumor growth. J Biol Chem 1999;274:1573–1580.

    Article  PubMed  CAS  Google Scholar 

  163. Habener JF. Cyclic AMP response element binding proteins: a cornucopia of transcription factors. Mol Endocrinol 1990;4:1087–1094.

    PubMed  CAS  Google Scholar 

  164. Park YG, Park S, Lim SO, et al. Reduction in cyclin D1/Cdk4/retinoblastoma protein signaling by CRE-decoy oligonucleotide. Biochem Biophys Res Commun 2001;281:1213–1219.

    Article  PubMed  CAS  Google Scholar 

  165. Liu WM, Scott KA, Shahin S, Propper DJ. The in vitro effects of CRE-decoy oligonucleotides in combination with conventional chemotherapy in colorectal cancer cell lines. Eur J Biochem 2004;271(13):2773–2781.

    Article  PubMed  CAS  Google Scholar 

  166. Cho YS, Park YG, Lee YN, et al. Extracellular protein kinase A as a cancer biomarker: its expression by tumor cells and reversal by a myristate-lacking Calpha and RIIbeta subunit overexpression. Proc Natl Acad Sci USA 2000;97:835–840.

    Article  PubMed  CAS  Google Scholar 

  167. Cho YS, Lee YN, Cho-Chung YS. Biochemical characterization of extracellular cAMPdependent protein kinase as a tumor marker. Biochem Biophys Res Commun 2000;278: 679–684.

    Article  PubMed  CAS  Google Scholar 

  168. Cvijic ME, Kita T, Shih W, DiPaola RS, Chin KV. Extracellular catalytic subunit activity of the cAMP-dependent protein kinase in prostate cancer. Clin Cancer Res 2000;6(6): 2309–2317.

    PubMed  CAS  Google Scholar 

  169. Kita T, Goydos J, Reitman E, et al. Extracellular cAMP-dependent protein kinase (ECPKA) in melanoma. Cancer Lett 2004;208:187–191.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cellular Biochemistry Section, Basic Research Laboratory, CCR, National Cancer Institute, Bethesda, MD

    Maria V. Nesterova PhD

  2. Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD

    Yoon S. Cho-Chung MD, PhD

Authors
  1. Maria V. Nesterova PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoon S. Cho-Chung MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, TX

    Rakesh Srivastava

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Nesterova, M.V., Cho-Chung, Y.S. (2006). Significance of Protein Kinase A in Cancer. In: Srivastava, R. (eds) Apoptosis, Cell Signaling, and Human Diseases. Humana Press. https://doi.org/10.1007/978-1-59745-199-4_1

Download citation

Publish with us

Policies and ethics

Search

Navigation