Skip to main content
SpringerLink
Log in

The Retinoids and Cancer Chemoprevention

  • Chapter
Cancer Chemoprevention

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The retinoids—natural and synthetic derivatives of vitamin A—play a role in cancer therapy and prevention. Their role in chemoprevention has been highlighted through the results of clinical and epidemiological studies in conjunction with basic research on retinoid mechanisms of action, advances in genomic information, novel organic synthesis of retinoid analogs, and availability of reliable model systems. This chapter focuses on the results of recent retinoid clinical cancer therapy and chemoprevention trials, reviews the current understanding of the molecular mechanism of retinoid action, discusses in vitro models used to study retinoid chemoprevention, and summarizes information on retinoid target genes. An understanding of the convergence of clinical and basic scientific advances in the retinoid field should lead to improved strategies to use these pharmacological agents in cancer therapy or chemoprevention.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Dmitrovsky E, Sporn MB. Pharmacology of cancer chemoprevention. Encyclopedia of Cancer. Academic Press, San Diego, CA, 2002, pp.449–456.

    Book  Google Scholar 

  2. Hong WK, Itri LM. Retinoids and human cancer, in The Retinoids: Biology, Chemistry, and Medicine, 2nd ed. Sporn MB, Roberts AB, Goodman DS, eds. Raven Press Ltd, New York, NY, 1994, pp.597–630.

    Google Scholar 

  3. Gudas LJ, Sporn MB, Roberts AB. Cellular biology and biochemistry of retinoids, in The Retinoids: Biology, Chemistry, and Medicine, 2nd ed. Sporn MB, Roberts AB, Goodman DS, eds. Raven Press Ltd, New York, NY, 1994, pp.443–520.

    Google Scholar 

  4. Moon RC, Mehta RG, Rao KVN. Retinoids and cancer in experimental animals, in The Retinoids: Biology, Chemistry, and Medicine, 2nd ed. Sporn MB, Roberts AB, Goodman DS, eds. Raven Press Ltd, New York, NY, 1994, pp.573–595.

    Google Scholar 

  5. Nason-Burchenal K, Dmitrovsky E. The retinoids: cancer therapy and prevention mechanisms, in Retinoids. The Biochemical and Molecular Basis of Vitamin A and Retinoid Action: Handbook of Experimental Pharmacology, vol. 139. Nau H, Blaner W, eds. Springer-Verlag, Berlin, Heidelberg, 1999, pp.301–322.

    Google Scholar 

  6. Miller WH Jr, Kakizuka A, Frankel SR, et al. Reverse transcription polymerase chain reaction for the rearranged retinoic acid receptor a clarifies diagnosis and detects minimal residual disease in acute promyelocytic leukemia. Proc Nall Acad Sci USA 1992;89:2694–2698.

    Article  CAS  Google Scholar 

  7. Lotan R, Xu XC, Lippman SM, et al. Suppression of retinoic acid receptor-Iβ in premalignant oral lesions and its up-regulation by isotretinoin. N Engl J Med 1995;332:1405–1410.

    Article  PubMed  CAS  Google Scholar 

  8. Collins SJ, Robertson KA, Mueller L. Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-a). Mol Cell Biol 1990;10:2154–2163.

    PubMed  CAS  Google Scholar 

  9. Spinella MJ, Kitareewan S, Mellado B, et al. Specific retinoid receptors cooperate to signal growth suppression and maturation of human embryonal carcinoma cells. Oncogene 1998;16:3471–3480.

    Article  PubMed  CAS  Google Scholar 

  10. Matthay KK, Villablanca JG, Seeger RC, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children’s Cancer Group. N Engl J Med 1999;341:1165–1173.

    Article  PubMed  CAS  Google Scholar 

  11. Hong WK, Endicott J, Itri LM, et al. 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med 1986;315:1501–1505.

    Article  PubMed  CAS  Google Scholar 

  12. Kraemer KH, DiGiovanna JJ, Moshell AN, et al. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 1988;318:1633–1637.

    Article  PubMed  CAS  Google Scholar 

  13. Meyskens FL Jr, Surwit E, Moon TE, et al. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. J Natl Cancer Inst 1994;86:539–543.

    Article  PubMed  Google Scholar 

  14. Hong WK, Lippman SM, Itri LM, et al. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 1990;323:795–801.

    Article  PubMed  CAS  Google Scholar 

  15. Veronesi U, De Palo G, Marubini E, et al. Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. J Natl Cancer Inst 1999;91:1847–1856.

    Article  PubMed  CAS  Google Scholar 

  16. Muto Y, Moriwaki H, Ninomiya M, et al. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med 1996;334:1561–1567.

    Article  PubMed  CAS  Google Scholar 

  17. Wolbach SB, Howe PR. Tissue changes following deprivation of fat-soluble vitamin A. J Exp Med 1925;42:753–777.

    Article  PubMed  CAS  Google Scholar 

  18. Langenfeld J, Lonardo F, Kiyokawa H, et al. Inhibited transformation of immortalized human bronchial epithelial cells by retinoic acid is linked to cyclin E down-regulation. Oncogene 1996;13:1983–1990.

    PubMed  CAS  Google Scholar 

  19. Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and diseasespecific mortality in the general population. J Nall Cancer Inst 1993;85:1483–1492.

    Article  CAS  Google Scholar 

  20. Dragnev KH, Stover D, Dmitrovsky E. Lung cancer prevention: the guidelines. Chest 2003,123:60S–71S.

    Article  PubMed  Google Scholar 

  21. Pastorino U, Infante M, Maioli M, et al. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol 1993;11:1216–1222.

    PubMed  CAS  Google Scholar 

  22. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. The effect of vitamin E and fβ-carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029–1035.

    Article  Google Scholar 

  23. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with fβ-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996;334:1145–1149.

    Article  PubMed  CAS  Google Scholar 

  24. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of β carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150–1155.

    Article  PubMed  CAS  Google Scholar 

  25. Lippman SM, Lee JJ, Karp DD, et al. Randomized Phase III intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer. J Natl Cancer Inst 2001;93:605–618.

    Article  PubMed  CAS  Google Scholar 

  26. Virmani AK, Rathi A, Zochbauer-Muller S, et al. Promoter methylation and silencing of the retinoic acid receptor-fβ gene in lung carcinomas. J Natl Cancer Inst 2000;92:1303–1307.

    Article  PubMed  CAS  Google Scholar 

  27. Lehmann JM, Dawson MI, Hobbs PD, et al. Identification of retinoids with nuclear receptor subtype-selective activities. Cancer Res 1991;51:4804–4809.

    PubMed  CAS  Google Scholar 

  28. Lehmann JM, Jong L, Fanjul A, et al. Retinoids selective for retinoid X receptor response pathways. Science 1992;258:1944–1946.

    Article  PubMed  CAS  Google Scholar 

  29. Gottardis MM, Bischoff ED, Shirley MA, et al. Chemoprevention of mammary carcinoma by LGD 1069 (Targretin): an RXR-selective ligand. Cancer Res 1996;56:5566–5570.

    PubMed  CAS  Google Scholar 

  30. Heald P. The treatment of cutaneous T- cell lymphoma with a novel retinoid. Clin Lymphoma Suppl 2000;1:S45–S49.

    Article  Google Scholar 

  31. Khuri FR, Rigas JR, Figlin RA, et al. Multi-institutional phase I/II trial of oral bexarotene in combination with cisplatin and vinorelbine in previously untreated patients with advanced non-small-cell lung cancer. J Clin Oncol 2001;19:2626–2637.

    PubMed  CAS  Google Scholar 

  32. Heyman RA, Mangelsdorf DJ, Dyck JA, et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992;68:397–406.

    Article  PubMed  CAS  Google Scholar 

  33. Levin AA, Sturzenbecker LJ, Kazmer S, et al. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature 1992;355:359–361.

    Article  PubMed  CAS  Google Scholar 

  34. Dahl AR, Grossi IM, Houchens DP, et al. Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer chemopreventive agent in All mice at low doses: a pilot study. Clin Cancer Res 2000; 6:3015–3024.

    PubMed  CAS  Google Scholar 

  35. Lonardo F, Dragnev KH, Freemantle SJ, et al. Evidence for the epidermal growth factor receptor as a target for lung cancer prevention. Clin Cancer Res 2002;8:54–60.

    PubMed  CAS  Google Scholar 

  36. Kitareewan S, Spinella MJ, Allopenna J, et al. 4HPR triggers apoptosis but not differentiation in retinoid sensitive and resistant human embryonal carcinoma cells through an RARy independent pathway. Oncogene 1999;18:5747–5755.

    Article  PubMed  CAS  Google Scholar 

  37. Delia D, Aiello A, Lombardi L, et al. N-(4-hydroxyphenyl)retinamide induces apoptosis of malignant hemopoietic cell lines including those unresponsive to retinoic acid. Cancer Res 1993;53:6036–6041.

    PubMed  CAS  Google Scholar 

  38. Oridate N, Suzuki S, Higuchi M, et al. Involvement of reactive oxygen species in N-(4-hydroxyphenyl)retinamide-induced apoptosis in cervical carcinoma cells. J Natl Cancer Inst 1997;89:1191–1198.

    Article  PubMed  CAS  Google Scholar 

  39. Fanjul AN, Delia D, Pierotti MA, et al. 4-Hydroxyphenyl retinamide is a highly selective activator of retinoid receptors. J Biol Chem 1996;271:22,441–22,446.

    CAS  Google Scholar 

  40. Delia D, Aiello A, Meroni L, et al. Role of antioxidants and intracellular free radicals in retinamide-induced cell death. Carcinogenesis 1997;18:943–948.

    Article  PubMed  CAS  Google Scholar 

  41. Fanjul A, Dawson MI, Hobbs PD, et al. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature 1994;372:107–111.

    Article  PubMed  CAS  Google Scholar 

  42. Blaner WS, Piantedosi R, Sykes A, Vogel S. Retinoic acid synthesis and metabolism, in Retinoids. The Biochemical and Molecular Basis of Vitamin A and Retinoid Action: Handbook of Experimental Pharmacology, vol. 139. Nau H, Blaner W, eds. Springer-Verlag, Berlin, Heidelberg, 1999, pp.117–152.

    Google Scholar 

  43. Mangelsdorf DJ, Evans RM. Retinoid receptors as transcrip-tion factors, in Transcriptional Regulation. McKnight SL, Yamamoto KR, eds. Cold Spring Harbor Laboratory Press, New York, 1992, pp.1137–1167.

    Google Scholar 

  44. Piedrafita FJ, Pfahl M. Nuclear retinoid receptors and mechanisms of action, in Retinoids. The Biochemical and Molecular Basis of Vitamin A and Retinoid Action: Handbook of Experimental Pharmacology, vol. 139. Nau H, Blaner W, eds. Springer-Verlag, Berlin, Heidelberg, 1999, pp.153–184.

    Google Scholar 

  45. Mukherjee R, Davies PJ, Crombie DL, et al. Sensitization of diabetic and obese mice to insulin by retinoid X receptor angonists. Nature 1997;386:407–410.

    Article  PubMed  CAS  Google Scholar 

  46. Torrisi R, Decensi A. Fenretinide and cancer prevention. Curr Oncol Rep 2000;2:263–270.

    Article  PubMed  CAS  Google Scholar 

  47. Wu JM, DiPietrantonio AM, Hsieh TC. Mechanism of fenretinide (4-HPR)-induced cell death. Apoptosis 2001;6:377–388.

    Article  PubMed  CAS  Google Scholar 

  48. Schadendorf D, Kern MA, Artuc M, et al. Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo. J Cell Biol 1996;135(6Pt2):1889–1898.

    Article  PubMed  CAS  Google Scholar 

  49. Murakami K, Sakukawa R, Sano M, et al. Inhibition of angiogenesis and intrahepatic growth of colon cancer by TAC-101. Clin Cancer Res 1999;5:2304–2310.

    PubMed  CAS  Google Scholar 

  50. Oikawa T, Murakami K, Sano M, et al. A potential use of a synthetic retinoid TAC-101 as an orally active agent that blocks angiogenesis in liver metastases of human stomach cancer cells. Jpn J Cancer Res 2001;92:1225–1234.

    Article  PubMed  CAS  Google Scholar 

  51. MaCaffery P, Drager UC. Regulation of retinoic acid signaling in the embryonic nervous system: a master differentiation factor. Cytokine Growth Factor Rev 2000;11:233–249.

    Article  Google Scholar 

  52. Tamayo P, Slonim D, Mesirov J, et al. Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation. Proc Natl Acad Sci USA 1999;96:2907–2912.

    Article  PubMed  CAS  Google Scholar 

  53. Freemantle SJ, Kerley JS, Olsen SL, et al. Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embyronal carcinoma cells. Oncogene 2002;25:2880–2889.

    Article  Google Scholar 

  54. Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995;377:454–457.

    Article  PubMed  CAS  Google Scholar 

  55. Horlein AJ, Naar AM, Heinzel T, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995;377:397–404.

    Article  PubMed  CAS  Google Scholar 

  56. Xu L, Glass CK, Rosenfeld MG. Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dey 1999;9:140–147.

    Article  CAS  Google Scholar 

  57. Urnov FD, Wolffe AP, Guschin D. Molecular mechanisms of corepressor function. Curr Top Microbiol Immunol 2001;254:1–33.

    Article  PubMed  CAS  Google Scholar 

  58. Privalsky ML. Regulation of SMRT and N-CoR corepressor function. Curr Top Microbiol Immunol 2001;254:117–136.

    Article  PubMed  CAS  Google Scholar 

  59. Xu W, Chen H, Du K, Asahara H, et al. A transcriptional switch mediated by cofactor methylation. Science 2001;294:2507–2511.

    Article  PubMed  CAS  Google Scholar 

  60. Rosenfeld MG, Glass CK. Coregulator codes of transcriptional regulation by nuclear receptors. J Biol Chem 2001;276:36,865–36,868.

    Article  CAS  Google Scholar 

  61. Naar AM, Lemon BD, Tjian R. Transcriptional coactivator complexes. Annu Rev Biochem 2001;70:475–501.

    Article  PubMed  CAS  Google Scholar 

  62. Rachez C, Freedman LP. Mediator complexes and transcription. Curr Opin Cell Biol 2001;13:274–280.

    Article  PubMed  CAS  Google Scholar 

  63. Rachez C, Lemon BD, Suldan Z, et al. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 1999;398:824–828.

    Article  PubMed  CAS  Google Scholar 

  64. Wallberg AE, Neely KE, Hassan AH, et al. Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor tau 1 activation domain. Mol Cell Biol 2000;20: 2004–2013.

    Article  PubMed  CAS  Google Scholar 

  65. Lemon B, Inouye C, King DS, Tjian R. Selectivity of chromatin-remodelling cofactors for ligand-activated transcription. Nature 2001;414:924–928.

    Article  PubMed  CAS  Google Scholar 

  66. Boyle JO, Langenfeld J, Lonardo F, et al. Cyclin D1 proteolysis: a retinoid chemoprevention signal in normal, immortalized, and transformed hurhan bronchial epithelial cells. J Natl Cancer Inst 1999;91:373–379.

    Article  PubMed  CAS  Google Scholar 

  67. Langenfeld J, Kiyokawa H, Sekula D, et al. Posttranslational regulation of cyclin D1 by retinoic acid: a chemoprevention mechanism. Proc Natl Acad Sci USA 1997;94:12,070–12,074.

    Article  CAS  Google Scholar 

  68. Spinella MJ, Freemantle SJ, Sekula D, et al. Retinoic acid promotes ubiquitination and proteolysis of cyclin D1 during induced tumor cell differentiation. J Biol Chem 1999;274:22,013–22,018.

    Article  CAS  Google Scholar 

  69. Dragnev KH, Pitha-Rowe IP, Ma Y, et al. Specific chemopreventive agents target proteasomal degradation of G1 cyclins: implications for combination therapy. Clin Cancer Res, in Press.

    Google Scholar 

  70. Brambilla E, Gazzeri S, Moro D, et al. Alterations of Rb pathway (Rb-p 16INK4-cyclin D1) in preinvasive bronchial lesions. Clin Cancer Res 1999;5:243–250.

    PubMed  CAS  Google Scholar 

  71. Lonardo F, Rusch V, Langenfeld J, et al. Overexpression of cyclins D1 and E is frequent in bronchial preneoplasia and precedes squamous cell carcinoma development. Cancer Res 1999;59:2470–2476.

    PubMed  CAS  Google Scholar 

  72. Lonardo F, Dragnev KH, Freemantle SJ, et al. Evidence for the epidermal growth factor receptor as a target for lung cancer prevention. Clin Cancer Res 2002;8:54–60.

    PubMed  CAS  Google Scholar 

  73. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183–232.

    Article  PubMed  CAS  Google Scholar 

  74. Rusch V, Mendelsohn J, Dmitrovsky E. The epidermal growth factor receptor and its ligands as therapeutic targets in human tumors. Cytokine Growth Factor Rev 1996;7:133–141.

    Article  PubMed  CAS  Google Scholar 

  75. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 2001;7:2958–2970.

    PubMed  CAS  Google Scholar 

  76. Rak J, Yu JL, Klement G, Kerbel RS. Oncogenes and angiogenesis: signaling three-dimensional tumor growth. J Investig Dermatol Symp Proc 2000;5:24–33.

    Article  PubMed  CAS  Google Scholar 

  77. Sueoka N, Lee HY, Walsh GL, et al. Posttranslational mechanisms contribute to the suppression of specific cyclin: CDK complexes by all-trans retinoic acid in human bronchial epithelial cells. Cancer Res 1999;59:3838–4438.

    PubMed  CAS  Google Scholar 

  78. Soria JC, Moon C, Wang L, et al. Effects of N-(4-Hydroxyphenyl)retinamide on hTERT expression in the bronchial epithelium of cigarette smokers. J Natl Cancer Inst 2001;93:1257–1263.

    Article  PubMed  CAS  Google Scholar 

  79. Melnick A, Licht JD. Deconstructing a disease: its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 1999;3167–3215.

    Google Scholar 

  80. Lanotte M, Martin-Thouvenin V, Najman S, et al. NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Blood 1991;77:1080–1086.

    PubMed  CAS  Google Scholar 

  81. Nason-Burchenal K, Maerz W, Albanell J, et al. Common defects of different retinoic acid resistant promyelocytic leukemia cells are persistent telomerase activity and nuclear body disorganization. Differentiation 1997;61:321–331.

    Article  PubMed  CAS  Google Scholar 

  82. Shao W, Benedetti L, Lamph WW, et al. A retinoid-resistant acute promyelocytic leukemia subclone expresses a dominant negative PML-RARa mutation. Blood 1997;89:4282–4289.

    PubMed  CAS  Google Scholar 

  83. Kitamura K, Kiyoi H, Yoshida H, et al. Mutant AF-2 domain of PML-RARa in retinoic acid-resistant NB4 cells: differentiation induced by RA is triggered directly through PML-RARa and its down-regulation in acute promyelocytic leukemia. Leukemia 1997;11:1950–1956.

    Article  PubMed  CAS  Google Scholar 

  84. Nason-Burchenal K, Allopenna J, Begue A, et al. Targeting of PML/RARα is lethal to retinoic acid-resistant promyelocytic leukemia cells. Blood 1998;92:1758–1767.

    PubMed  CAS  Google Scholar 

  85. Early E, Moore MA, Kakizuka A, et al. Transgenic expression of PML/RARa impairs myelopoiesis. Proc Natl Acad Sci USA 1996;93:7900–7904.

    Article  PubMed  CAS  Google Scholar 

  86. Grisolano JL, Wesselschmidt RL, Pelicci PG, Ley TJ. Altered myeloid development and acute leukemia in trans-genic mice expressing PML-RARa under control of cathepsin G regulatory sequences. Blood 1997;89:376–387.

    PubMed  CAS  Google Scholar 

  87. Brown D, Kogan S, Lagasse E, et al. A PMLRARa-transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci USA 1997;94:2551–2556.

    Article  PubMed  CAS  Google Scholar 

  88. He LZ, Tribioli C, Rivi R, et al. Acute leukemia with promyelocytic features in PML/RARα transgenic mice. Proc Natl Acad Sci USA 1997;94:5302–5307.

    Article  PubMed  CAS  Google Scholar 

  89. Salomoni P, Pandolfi PP. The role of PML in tumor suppres-sion. Cell 2002;108:165–170.

    Article  PubMed  CAS  Google Scholar 

  90. Pollock JL, Westervelt P, Kurichety AK, et al. A bcr-3 isoform of RARa-PML potentiates the development of PML-RARa-driven acute promyelocytic leukemia. Proc Natl Acad Sci USA 1999;96:15,103–15,108.

    Article  CAS  Google Scholar 

  91. Ahn MJ, Nason-Burchenal K, Moasser MM, Dmitrovsky E. Growth suppression of acute promyelocytic leukemia cells having increased expression of the non-rearranged alleles: RAR alpha or PML. Oncogene 1995;10:2307–2314.

    PubMed  CAS  Google Scholar 

  92. Mu ZM, Chin KV, Liu JH, et al. PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol Cell Biol 1994;14:6858–6867.

    PubMed  CAS  Google Scholar 

  93. Nason-Burchenal K, Takle G, Pace U, et al. Targeting the PML/RARα translocation product triggers apoptosis in promyelocytic leukemia cells. Oncogene 1998;17:1759–1768.

    Article  PubMed  CAS  Google Scholar 

  94. Pace U, Bockman JM, MacKay BJ, et al. A ribozyme which discriminates in vitro between PML/RARα, the t(15;17)-associated fusion RNA of acute promyelocytic leukemia, and PML and RARα, the transcripts from the nonrearranged alleles. Cancer Res 1994;54:6365–6369.

    PubMed  CAS  Google Scholar 

  95. Lin RI, Nagy L, Inoue S, et al. Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature 1998;391:811–814.

    Article  PubMed  CAS  Google Scholar 

  96. Grignani F, De Matteis S, Nervi C, et al. Fusion proteins of the retinoic acid receptor-α recruit histone deacetylase in promyelocytic leukaemia. Nature 1998;391:815–818.

    Article  PubMed  CAS  Google Scholar 

  97. Di Croce L, Raker VA, Corsaro M, et al. Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 2002;295:1079–1082.

    Article  PubMed  Google Scholar 

  98. Kitareewan S, Pitha-Rowe I, Sekula D, et al. UBE 1 L is a retinoid target that triggers PML/RARα degradation and apoptosis in acute promyelocytic leukemia. Proc Natl Acad Sci USA 2002;99:3806–3811.

    Article  PubMed  CAS  Google Scholar 

  99. Duprez E, Ruchaud S, Houge G, et al. A retinoid acid ‘resistant’ t(15;17) acute promyelocytic leukemia cell line: isolation, morphological, immunological, and molecular features. Leukemia 1992;6:1281–1287.

    PubMed  CAS  Google Scholar 

  100. Dermime S, Grignani F, Clerici M, et al. Occurrence of resistance to retinoic acid in the acute promyelocytic leukemia cell line NB4 is associated with altered expression of the pml/RAR alpha protein. Blood 1993;82:1573–1577.

    PubMed  CAS  Google Scholar 

  101. Ruchaud S, Duprez E, Gendron MC, et al. Two distinctly regulated events, priming and triggering, during retinoid-induced maturation and resistance of NB4 promyelocytic leukemia cell line. Proc Natl Acad Sci USA 1994;91:8428–8432.

    Article  PubMed  CAS  Google Scholar 

  102. Andrews PW, Damjanov I, Simon D, et al. Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro. Lab Invest 1984;50:147–162.

    PubMed  CAS  Google Scholar 

  103. Dmitrovsky E, Moy D, Miller WH Jr, et al. Retinoic acid causes a decline in TGF-alpha expression, cloning efficiency, and tumorigenicity in a human embryonal cancer cell line. Oncogene Res 1990;5:233–239.

    PubMed  CAS  Google Scholar 

  104. Moasser MM, Khoo KS, Maerz WJ, et al. Derivation and characterization of retinoid-resistant human embryonal carcinoma cells. Differentiation 1996;60:251–257.

    Article  PubMed  CAS  Google Scholar 

  105. Moasser MM, Reuter VE, Dmitrovsky E. Overexpression of the retinoic acid receptor gamma directly induces terminal differentiation of human embryonal carcinoma cells. Oncogene 1995;10:1537–1543.

    PubMed  CAS  Google Scholar 

  106. Kerley JS, Olsen SL, Freemantle SJ, Spinella MJ. Transcriptional activation of the nuclear receptor corepressor RIP 140 by retinoic acid: a potential negative-feedback regulatory mechanism. Biochem Biophys Res Commun 2001;285:969–975.

    Article  PubMed  CAS  Google Scholar 

  107. Liu TX, Zhang JW, Tao J, et al. Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells. Blood 2000;96:1496–1504.

    PubMed  CAS  Google Scholar 

  108. Gudkov AV, Zelnick CR, Kazarov AR, et al. Isolation of genetic suppressor elements, inducing resistance to topoisomerase II-interactive cytotoxic drugs, from human topoisomerase II cDNA. Proc Natl Acad Sci USA 1993;90:3231–3235.

    Article  PubMed  CAS  Google Scholar 

  109. Deiss LP, Kimchi A. A genetic tool used to identify thioredoxin as a mediator of a growth inhibitory signal. Science 1991;252:117–120.

    Article  PubMed  CAS  Google Scholar 

  110. Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001;411:494–498.

    Article  PubMed  CAS  Google Scholar 

  111. Nervi C, Ferrara FF, Fanelli M, et al. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARa fusion protein. Blood 1998;92:2244–2251.

    PubMed  CAS  Google Scholar 

  112. Raelson JV, Nervi C, Rosenauer A, et al. The PML/RARα oncoprotein is a direct molecular target of retinoic acid in acute promyelocytic leukemia cells. Blood 1996;88:2826–2832.

    PubMed  CAS  Google Scholar 

  113. Yoshida H, Kitamura K, Tanaka K, et al. Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway. Cancer Res 1996;56:2945–2948.

    PubMed  CAS  Google Scholar 

  114. Zhu J, Gianni M, Kopf E, et al. Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor a (RARa) and oncogenic RARa fusion proteins. Proc Natl Acad Sci USA 1999;96:14,807–14,812.

    CAS  Google Scholar 

  115. Chih DY, Chumakov AM, Park DJ, et al. Modulation of mRNA expression of a novel human myeloid-selective CCAAT/enhancer binding protein gene (C/EBP∈). Blood 1997;90:2987–2994

    PubMed  CAS  Google Scholar 

  116. Yuan W, Krug RM. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J 2001;20:362–371.

    Article  PubMed  CAS  Google Scholar 

  117. Loeb KR, Haas AL. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem 1992;267:7806–7813.

    PubMed  CAS  Google Scholar 

  118. Narasimhan J, Potter JL, Haas AL. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. J Biol Chem 1996;271:324–330.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Sutisak Kitareewan PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ian Pitha-Rowe BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Ma BM
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sarah J. Freemantle PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ethan Dmitrovsky MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National Institutes of Health, Rockville, MD, USA

    Gary J. Kelloff MD  & Ernest T. Hawk MD, MPH  & 

  2. CCS Associates, Mountain View, CA, USA

    Caroline C. Sigman PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kitareewan, S., Pitha-Rowe, I., Ma, Y., Freemantle, S.J., Dmitrovsky, E. (2004). The Retinoids and Cancer Chemoprevention. In: Kelloff, G.J., Hawk, E.T., Sigman, C.C. (eds) Cancer Chemoprevention. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-767-3_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-767-3_18

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-342-8

  • Online ISBN: 978-1-59259-767-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation