Skip to main content
SpringerLink
Log in

Activins, Inhibins, and Bone Morphogenetic Proteins as Modulators and Biomarkers of Prostate Cancer Progression

  • Chapter
Transforming Growth Factor-β in Cancer Therapy, Volume I

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

  • 1585 Accesses

Abstract

The transforming growth factor-β (TGF-β) superfamily consists of over 35 structurally related proteins, which regulate a myriad of cellular processes. Signaling by these growth regulatory molecules is initiated by ligand-induced hetero-oligomerization of distinct type II and type I serine/threonine kinase receptors that activate receptor-activated Smad proteins as well as Smad-independent pathways. TGF-β-related ligands and receptors are expressed in the prostate gland and aberrant expression and function of this class of signaling molecules are likely to regulate development and tumorigenesis of the prostate. The functional significance of TGF-β in prostate cancer has been reviewed in several articles. The objective of this review is to evaluate the expression and functional significance of activins, inhibins, and BMP signaling in prostate development and tumorigenesis, and their role as modulators and biomarkers of prostate cancer progression.

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 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 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. Hayward SW, Cunha GR. The prostate: development and physiology. Radiol Clin North Am 2000; 38:1–14.

    Article  CAS  PubMed  Google Scholar 

  2. Aumuller G. Morphologic and endocrine aspects of prostatic function. Prostate 1983;4:195–214.

    Article  CAS  PubMed  Google Scholar 

  3. Aumuller G. Morphologic and regulatory aspects of prostatic function. Anat Embryol (Berl) 1989; 179:519–531.

    Article  CAS  Google Scholar 

  4. Cunha GR, Donjacour AA, Sugimura Y. Stromal-epithelial interactions and heterogeneity of proliferative activity within the prostate. Biochem Cell Biol 1986;64:608–614.

    Article  CAS  PubMed  Google Scholar 

  5. Cunha GR. Role of mesenchymal-epithelial interactions in normal and abnormal development of the mammary gland and prostate. Cancer 1994;74:1030–1044.

    Article  CAS  PubMed  Google Scholar 

  6. Kumar VL, Majumder PK. Prostate gland: structure, functions and regulation. Int Urol Nephrol 1995;27:231–243.

    Article  CAS  PubMed  Google Scholar 

  7. Wilson JD. The pathogenesis of benign prostatic hyperplasia. Am J Med 1980;68:745–756.

    Article  CAS  PubMed  Google Scholar 

  8. Griffiths K, Eaton CL, Harper ME, Peeling B, Davies B. Steroid hormones and the pathogenesis of benign prostatic hyperplasia. Eur Urol 20 Suppl 1991;1:68–77.

    Google Scholar 

  9. Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl 1989;2:33–50.

    Article  CAS  PubMed  Google Scholar 

  10. Cotran R, Kumar V, Collins T. Pathologic Basis of Disease, 6th Edition ed., Saunders WB Company 1974.

    Google Scholar 

  11. Taneja SS. The role of androgen receptor coactivators in prostate cancer growth. Prostate Cancer Prostatic Dis 2000;3:S38.

    Article  PubMed  Google Scholar 

  12. Huang H, Tindall DJ. The role of the androgen receptor in prostate cancer. Crit Rev Eukaryot Gene Expr 2002;12:193–207.

    Article  CAS  PubMed  Google Scholar 

  13. Debes JD, Tindall DJ. The role of androgens and the androgen receptor in prostate cancer. Cancer Lett 2002;187:1–7.

    Article  CAS  PubMed  Google Scholar 

  14. Suzuki H, Ito H. Role of androgen receptor in prostate cancer. Asian J Androl 1999;1:81–85.

    CAS  PubMed  Google Scholar 

  15. Jenster G. The role of the androgen receptor in the development and progression of prostate cancer, Semin Oncol 1999;26:407–421.

    CAS  PubMed  Google Scholar 

  16. Kim HG, Kassis J, Souto JC, Turner T, Wells A. EGF receptor signaling in prostate morphogenesis and tumorigenesis, Histol Histopathol 1999;14:1175–1182.

    CAS  PubMed  Google Scholar 

  17. Thompson TC. Growth factors and oncogenes in prostate cancer. Cancer Cells 1990;2:345–354.

    CAS  PubMed  Google Scholar 

  18. Wong YC, Wang YZ. Growth factors and epithelial-stromal interactions in prostate cancer development. Int Rev Cytol 2000;199:65–116.

    Article  CAS  PubMed  Google Scholar 

  19. Urwin GH, Percival RC, Harris S, Beneton MN, Williams JL, Kanis JA. Generalised increase in bone resorption in carcinoma of the prostate. Br J Urol 1985;57:721–723.

    Article  CAS  PubMed  Google Scholar 

  20. Percival RC, Urwin GH, Harris S, et. al. Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption. Eur J Surg Oncol 1987;13:41–49.

    CAS  PubMed  Google Scholar 

  21. Vinholes J, Coleman R, Eastell R. Effects of bone metastases on bone metabolism: implications for diagnosis, imaging and assessment of response to cancer treatment. Cancer Treat Rev 1996;22:289–331.

    Article  CAS  PubMed  Google Scholar 

  22. Berruti A, Piovesan A, Torta M, et al. Biochemical evaluation of bone turnover in cancer patients with bone metastases: relationship with radiograph appearances and disease extension. Br J Cancer 1996;73:1581–1587.

    CAS  PubMed  Google Scholar 

  23. Logothetis CJ, Lin SH. Osteoblasts in prostate cancer metastasis to bone. Nat Rev Cancer 2005; 5:21–28.

    Article  CAS  PubMed  Google Scholar 

  24. Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem 2004;91:718–729.

    Article  CAS  PubMed  Google Scholar 

  25. Sakuma R, Ohnishi Yi Y, Meno C, et al. Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion. Genes Cells 2002;7:401–412.

    Article  CAS  PubMed  Google Scholar 

  26. Ying SY. Inhibins, activins follistatins J. Steroid Biochem 1989;33:705–713.

    Article  CAS  Google Scholar 

  27. Yamaguchi Y, Mann DM, Ruoslahti E, Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 1990;346:281–284.

    Article  CAS  PubMed  Google Scholar 

  28. Schneyer A, Tortoriello D, Sidis Y, Keutmann H, Matsuzaki T, Holmes W. Follistatin-related protein (FSRP): a new member of the follistatin gene family, Mol Cell Endocrinol 2001;180:33–38.

    Article  CAS  PubMed  Google Scholar 

  29. Massagué J. TGF-beta signal transduction. Annu Rev Biochem 1998;67:753–791.

    Article  PubMed  Google Scholar 

  30. Balemans W, Van Hul W. Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. Dev Biol 2002;250:231–250.

    CAS  PubMed  Google Scholar 

  31. Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factorbeta superfamily. Endocr Rev 2002;23:787–823.

    Article  CAS  PubMed  Google Scholar 

  32. Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science 2002;296:1646–1647.

    Article  CAS  PubMed  Google Scholar 

  33. Segev DL, Ha TU, Tran TT, et al. Mullerian inhibiting substance inhibits breast cancer cell growth through an NFkappa B-mediated pathway. J Biol Chem 2000;275:28,371–28,379.

    Article  CAS  PubMed  Google Scholar 

  34. Sovak MA, Arsura M, Zanieski G, Kavanagh KT, Sonenshein GE. The inhibitory effects of transforming growth factor betal on breast cancer cell proliferation are mediated through regulation of aberrant nuclear factor-kappaB/Rel expression. Cell Growth Differ 1999;10:537–544.

    CAS  PubMed  Google Scholar 

  35. Bello-DeOcampo D, Tindall DJ. TGF-betal/Smad signaling in prostate cancer. Curr Drug Targets 2003;4:197–207.

    Article  CAS  PubMed  Google Scholar 

  36. Danielpour D. Functions and regulation of transforming growth factor-beta (TGF-beta) in the prostate. Eur J Cancer 2005;41:846–857.

    Article  CAS  PubMed  Google Scholar 

  37. Wikstrom P, Bergh A, Damber JE. Transforming growth factor-beta1 and prostate cancer. Scand J Urol Nephrol 2000;34:85–94.

    Article  CAS  PubMed  Google Scholar 

  38. Wikstrom P, Damber J, Bergh A. Role of transforming growth factor-beta1 in prostate cancer. Microsc Res Tech 2001;52:411–419.

    Article  CAS  PubMed  Google Scholar 

  39. Lee C, Sintich SM, Mathews EP, et al. Transforming growth factor-beta in benign and malignant prostate. Prostate 1999;39:285–290.

    Article  CAS  PubMed  Google Scholar 

  40. Ying SY. Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocr Rev 1988;9:267–293.

    Article  CAS  PubMed  Google Scholar 

  41. Fang J, Yin W, Smiley E, Wang SQ, Bonadio J. Molecular cloning of the mouse activin beta E subunit gene. Biochem Biophys Res Commun 1996;228:669–674.

    Article  CAS  PubMed  Google Scholar 

  42. Lau AL, Kumar TR, Nishimori K, Bonadio J, Matzuk MM, Activin betaC and betaE genes are not essential for mouse liver growth, differentiation, and regeneration. Mol Cell Biol 2000;20:6127–6137.

    Article  CAS  PubMed  Google Scholar 

  43. Lau AL, Nishimori K, Matzuk MM. Structural analysis of the mouse activin beta C gene. Biochim Biophys Acta 1996;1307:145–148.

    PubMed  Google Scholar 

  44. Oda S, Nishimatsu S, Murakami K, Ueno N. Molecular cloning and functional analysis of a new activin beta subunit: a dorsal mesoderm-inducing activity in Xenopus. Biochem Biophys Res Commun 1995; 210:581–588.

    Article  CAS  PubMed  Google Scholar 

  45. de JP Winter, ten Dijke P, de CJ Vries, et al. Follistatins neutralize activin bioactivity by inhibition of activin binding to its type II receptors. Mol Cell Endocrinol 1996;116:105–114.

    Article  PubMed  Google Scholar 

  46. Schneyer AL, Rzucidlo DA, Sluss PM, Crowley WF, Jr. Characterization of unique binding kinetics of follistatin and activin or inhibin in serum. Endocrinology 1994;135:667–674.

    Article  CAS  PubMed  Google Scholar 

  47. Welt C, YSidis, Keutmann H, Schneyer A. Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium, Exp Biol Med (Maywood) 2002;227:724–752.

    CAS  Google Scholar 

  48. de DM Kretser, Meinhardt A, Meehan T, Phillips DJ, O’Bryan MK, Loveland KA The roles of inhibin and related peptides in gonadal function. Mol Cell Endocrinol 2000;161:43–46.

    Article  PubMed  Google Scholar 

  49. Chen YG, Lui HM, Lin SL, Lee JM, Ying SY. Regulation of cell proliferation, apoptosis, and carcinogenesis by activin. Exp Biol Med (Maywood) 2002;227:75–87.

    CAS  Google Scholar 

  50. Risbridger GP, Schmitt JF, Robertson DM. Activins and inhibins in endocrine and other tumors. Endocr Rev 2001;22:836–858.

    Article  CAS  PubMed  Google Scholar 

  51. Ying SY, Zhang Z Furst B, Batres Y, Huang G, Li G. Activins and activin receptors in cell growth. Proc Soc Exp Biol Med 1997;214:114–122.

    CAS  PubMed  Google Scholar 

  52. Feng ZM, Madigan MB, Chen CL. Expression of type II activin receptor genes in the male and female reproductive tissues of the rat. Endocrinology 1993;132:2593–2600.

    Article  CAS  PubMed  Google Scholar 

  53. Risbridger GP, Thomas, Gurusinghe CJ, McFarlane JR. Inhibin-related proteins in rat prostate. J Endocrinol 1996;149:93–99.

    Article  CAS  PubMed  Google Scholar 

  54. Cancilla B, Jarred RA, Wang H, Mellor SL, Cunha GR, Risbridger GP. Regulation of prostate branching morphogenesis by activin A and follistatin. Dev Biol 2001;237:145–158.

    Article  CAS  PubMed  Google Scholar 

  55. Al-Omari A, Shidaifat F, Dardaka M. Castration induced changes in dog prostate gland associated with diminished activin and activin receptor expression. Life Sci 2005;77:2752–2759.

    Article  CAS  PubMed  Google Scholar 

  56. Kang Y, Reddi AH. Identification and cloning of a novel type I serine/threonine kinase receptor of the TGF-beta/BMP superfamily in rat prostate. Biochem Mol Biol Int 1996;40:993–1001.

    CAS  PubMed  Google Scholar 

  57. Ball EM, Risbridger GP. Activins as regulators of branching morphogenesis. Dev Biol 2001;238:1–12.

    Article  CAS  PubMed  Google Scholar 

  58. Wang BE, Shou J, Ross S, Koeppen H, De Sauvage FJ, Gao WQ. Inhibition of epithelial ductal branching in the prostate by sonic hedgehog is indirectly mediated by stromal cells. J Biol Chem 2003;278:18,506–18,513.

    Article  CAS  PubMed  Google Scholar 

  59. Lamm ML, Podlasek CA, Barnett DH, et al. Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev Biol 2001;232:301–314.

    Article  CAS  PubMed  Google Scholar 

  60. Dalkin AC, Gilrain JT, Bradshaw D, Myers CE. Activin inhibition of prostate cancer cell growth: selective actions on androgen-responsive LNCaP cells. Endocrinology 1996;137:5230–5235.

    Article  CAS  PubMed  Google Scholar 

  61. McPherson SJ, Thomas TZ, Wang H, Gurusinghe CJ, Risbridger GP. Growth inhibitory response to activin A and B by human prostate tumour cell lines, LNCaP and DU145. J Endocrinol 1997;154:535–545.

    Article  CAS  PubMed  Google Scholar 

  62. McPherson SJ, Mellor SL, Wang H, Evans LW, Groome NP, Risbridger GP. Expression of activin A and follistatin core proteins by human prostate tumor cell lines. Endocrinology 1999;140:5303–5309.

    Article  CAS  PubMed  Google Scholar 

  63. Thomas TZ, Wang H, Niclasen P, et al. Expression and localization of activin subunits and follistatins in tissues from men with high grade prostate cancer. J Clin Endocrinol Metab 1997;82:3851–3858.

    Article  CAS  PubMed  Google Scholar 

  64. van Schaik RH, Wierikx CD, Timmerman MA, et al. Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues. Br J Cancer 2000;82:112–117.

    Article  PubMed  Google Scholar 

  65. Carey JL, Sasur LM, Kawakubo H, et al. Mutually antagonistic effects of androgen and activin in the regulation of prostate cancer cell growth. Mol Endocrinol 2004;18:696–707.

    Article  CAS  PubMed  Google Scholar 

  66. Wang QF, Tilly KI, Tilly JL, et al. Activin inhibits basal and androgen-stimulated proliferation and induces apoptosis in the human prostatic cancer cell line. LNCaP, Endocrinology 1996;137:5476–5483.

    Article  CAS  Google Scholar 

  67. Zhang Z, Zhao Y, Batres Y, Lin MF, Ying SY. Regulation of growth and prostatic marker expression by activin A in an androgen-sensitive prostate cancer cell line LNCAP. Biochem Biophys Res Commun 1997;234:362–365.

    Article  CAS  PubMed  Google Scholar 

  68. Wang M, Liu A, Garcia FU, Rhim JS, Stearns ME. Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT. Int J Oncol 1999;14:1185–1195.

    CAS  PubMed  Google Scholar 

  69. Wang Q, Tabatabaei S, Planz B, Lin CW, Sluss PM. Identification of an activin-follistatin growth modulatory system in the human prostate: secretion and biological activity in primary cultures of prostatic epithelial cells. J Urol 1999;161:1378–1384.

    Article  CAS  PubMed  Google Scholar 

  70. Lin S, Ying SY. Differentially expressed genes in activin-induced apoptotic LNCaP cells. Biochem Biophys Res Commun 1999;257:187–192.

    Article  CAS  PubMed  Google Scholar 

  71. Ying SY, Chuong CM, Lin S. Suppression of activin-induced apoptosis by novel antisense strategy in human prostate cancer cells. Biochem Biophys Res Commun 1999;265:669–673.

    Article  CAS  PubMed  Google Scholar 

  72. Ying SY, Lin SL. Gene expression in precursor cells of prostate cancer associated with activin by combination of subtractive hybridization and microarray technologie. Biochem Biophys Res Commun 2004;313:104–109.

    Article  CAS  PubMed  Google Scholar 

  73. Nozawa M, Yomogida K, Kanno N, et al. Prostate-specific transcription factor hPSE is translated only in normal prostate epithelial cells. Cancer Res 2000;60:1348–1352.

    CAS  PubMed  Google Scholar 

  74. Tsujimoto Y, Nonomura N, Takayama H, et al. Utility of immunohistochemical detection of prostate-specific Ets for the diagnosis of benign and malignant prostatic epithelial lesions. Int J Urol 2002;9:167–172.

    Article  CAS  PubMed  Google Scholar 

  75. Mitas M, Mikhitarian K, Hoover L, et al. Prostate-Specific Ets (PSE) factor: a novel marker for detection of metastatic breast cancer in axillary lymph nodes. Br J Cancer 2002;86:899–904.

    Article  CAS  PubMed  Google Scholar 

  76. Sato N, Fukushima N, Maitra A, et al. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res 2003;63:3735–3742.

    CAS  PubMed  Google Scholar 

  77. Dutta A, Bell SP. Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 1997;13:293–332.

    Article  CAS  PubMed  Google Scholar 

  78. Tang D, Khaleque MA, Jones EL, et al. Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones 2005;10:46–58.

    Article  CAS  PubMed  Google Scholar 

  79. Jones EL, Zhao MJ, Stevenson MA, Calderwood SK. The 70 kilodalton heat shock protein is an inhibitor of apoptosis in prostate cancer. Int J Hyperthermia 2004;20:835–849.

    Article  CAS  PubMed  Google Scholar 

  80. Cornford PA, Dodson AR, Parsons KF, et al. Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Res 2000;60:7099–7105.

    CAS  PubMed  Google Scholar 

  81. Fujii Y, Kawakami S, Okada Y, Kageyama Y, Kihara K. Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells. Am J Physiol Endocrinol Metab 2004;286:E927–E931.

    Article  CAS  PubMed  Google Scholar 

  82. Chen G, Nomura M, Morinaga H, et al. Modulation of androgen receptor transactivation by FoxH1. A newly identified androgen receptor corepressor. J Biol Chem 2005;280:36,355–36,363.

    Article  CAS  PubMed  Google Scholar 

  83. Iwamura M, Hellman J, Cockett AT, Lilja H, Gershagen S. Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology 1996;48:317–325.

    Article  CAS  PubMed  Google Scholar 

  84. Cramer SD, Chen Z, Peehl DM. Prostate specific antigen cleaves parathyroid hormone-related protein in the PTH-like domain: inactivation of PTHrP-stimulated cAMP accumulation in mouse osteoblasts, J Urol 1996;156:526–531.

    Article  CAS  PubMed  Google Scholar 

  85. Hempen PM, Zhang L, Bansal RK, et al. Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers. Cancer Res 2003;63:994–999.

    CAS  PubMed  Google Scholar 

  86. Danila DC, Inder WJ, Zhang X, et al. Activin effects on neoplastic proliferation of human pituitary tumors. J Clin Endocrinol Metab 2000;85:1009–1015.

    Article  CAS  PubMed  Google Scholar 

  87. Rossmanith W, Chabicovsky M, Grasl-Kraupp B, Peter B, Schausberger E, Schulte-Hermann R. Follistatin overexpression in rodent liver tumors: a possible mechanism to overcome activin growth control. Mol Carcinog 2002;35:1–5.

    Article  CAS  PubMed  Google Scholar 

  88. Jeruss JS, Sturgis CD, Rademaker AW, Woodruff TK. Down-regulation of activin, activin receptors, and Smads in high-grade breast cancer. Cancer Res 2003;63:3783–3790.

    CAS  PubMed  Google Scholar 

  89. Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A. Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 1992;360:313–319.

    Article  CAS  PubMed  Google Scholar 

  90. Schmitt JF, Millar DS, Pedersen JS, et al. Hypermethylation of the inhibin alpha-subunit gene in prostate carcinoma. Mol Endocrinol 2002;16:213–220.

    Article  CAS  PubMed  Google Scholar 

  91. Risbridger GP, Mellor SL, McPherson SJ, Schmitt JF. The contribution of inhibins and activins to malignant prostate disease. Mol Cell Endocrinol 2001;180:149–153.

    Article  CAS  PubMed  Google Scholar 

  92. Ying SY, Zhang Z, Huang G. Expression and localization of inhibin/activin subunits and activin receptors in the normal rat prostate. Life Sci 1997;60:397–401.

    Article  CAS  PubMed  Google Scholar 

  93. Balanathan P, Ball EM, Wang H, Harris SE, Shelling AN, Risbridger GP. Epigenetic regulation of inhibin alpha-subunit gene in prostate cancer cell lines. J Mol Endocrinol 2004;32:55–67.

    Article  CAS  PubMed  Google Scholar 

  94. Risbridger GP, Ball EM, Wang H, Mellor SL, Peehl DM. Re-evaluation of inhibin alpha subunit as a tumour suppressor in prostate cancer. Mol Cell Endocrinol 2004;225:73–76.

    Article  CAS  PubMed  Google Scholar 

  95. Sheth NA, Hurkadli KS, Sathe VS, Sheth AR. Circulating levels of inhibin in cancer. Neoplasma 1984;31:315–321.

    CAS  PubMed  Google Scholar 

  96. Lappohn RE, Burger HG, Bouma J, Bangah M, Krans M, de HW Bruijn. Inhibin as a marker for granulosa-cell tumors. N Engl J Med 1989;321:790–793.

    Article  CAS  PubMed  Google Scholar 

  97. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004;22:233–241.

    Article  CAS  PubMed  Google Scholar 

  98. Harris SE, Harris MA, Mahy P, Wozney J, Feng JQ, Mundy GR. Prostate 1994;24:204–211.

    Article  CAS  PubMed  Google Scholar 

  99. Hamdy FC, Autzen P, Robinson MC, Horne CH, Neal DE, Robson CN. Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue. Cancer Res 1997;57:4427–4431.

    CAS  PubMed  Google Scholar 

  100. Barnes J, Anthony CT, Wall N, Steiner MS. Bone morphogenetic protein-6 expression in normal and malignant prostate. World J Urol 1995;13:337–343.

    Article  CAS  PubMed  Google Scholar 

  101. Bentley H, Hamdy FC, Hart KA, et al. Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. Br J Cancer 1992;66:1159–1163.

    CAS  PubMed  Google Scholar 

  102. Almahbobi G, Hedwards S, Fricout G, Jeulin D, Bertram JF, Risbridger GP. Computer-based detection of neonatal changes to branching morphogenesis reveals different mechanisms of and predicts prostate enlargement in mice haplo-insufficient for bone morphogenetic protein 4. J Pathol 2005;206:52–61.

    Article  PubMed  Google Scholar 

  103. Autzen P, Robson CN, Bjartell A, et al. Bone morphogenetic protein 6 in skeletal metastases from prostate cancer and other common human malignancies, Br J Cancer 1998;78:1219–1223.

    CAS  PubMed  Google Scholar 

  104. Dai J, Keller J, Zhang J, Lu Y, Yao Z, Keller ET. Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res 2005;65:8274–8285.

    Article  CAS  PubMed  Google Scholar 

  105. Tamada H, Kitazawa R, Gohji K, Kitazawa S. Epigenetic regulation of human bone morphogenetic protein 6 gene expression in prostate cancer. J Bone Miner Res 2001;16:487–496.

    Article  CAS  PubMed  Google Scholar 

  106. Thomas BG, Hamdy FC. Bone morphogenetic protein-6: potential mediator of osteoblastic metastases in prostate cancer. Prostate Cancer Prostatic Dis 2000;3:283–285.

    Article  CAS  PubMed  Google Scholar 

  107. Masuda H, Fukabori Y, Nakano K, Shimizu N, Yamanaka H. Expression of bone morphogenetic protein-7 (BMP-7) in human prostate. Prostate 2004;59:101–106.

    Article  CAS  PubMed  Google Scholar 

  108. Thomas R, Anderson WA, Raman V, Reddi AH. Androgen-dependent gene expression of bone morphogenetic protein 7 in mouse prostate. Prostate 1998;37:236–245.

    Article  CAS  PubMed  Google Scholar 

  109. Bottner M, Suter-Crazzolara C, Schober A, Unsicker K. Expression of a novel member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues. Cell Tissue Res 1999;297:103–110.

    Article  CAS  PubMed  Google Scholar 

  110. Thomas R, True LD, Lange PH, Vessella RL. Placental bone morphogenetic protein (PLAB) gene expression in normal, pre-malignant and malignant human prostate: relation to tumor development and progression. Int J Cancer 2001;93:47–52.

    Article  CAS  PubMed  Google Scholar 

  111. Kakehi Y, Segawa T, Wu XX, Kulkarni P, Dhir R, Getzenberg RH. Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia. Prostate 2004;59:351–356.

    Article  CAS  PubMed  Google Scholar 

  112. Paralkar VM, Vail AL, Grasser WA, et al. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family. J Biol Chem 1998;273:13,760–13,767.

    Article  CAS  PubMed  Google Scholar 

  113. Brubaker KD, Corey E, Brown LG, Vessella RL. Bone morphogenetic protein signaling in prostate cancer cell lines. J Cell Biochem 2004;91:151–160.

    Article  CAS  PubMed  Google Scholar 

  114. Tomari K, Kumagai T, Shimizu T, Takeda K. Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells. Int J Mol Med 2005;15:253–258.

    CAS  PubMed  Google Scholar 

  115. Horvath LG, Henshall SM, Kench JG, et al. Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression. Prostate 2004;59:234–242.

    Article  CAS  PubMed  Google Scholar 

  116. Lee KS, Kim HJ, Li QL, et al. Runx2 is a common target of transforming growth factor betal and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol 2000;20:8783–8792.

    Article  CAS  PubMed  Google Scholar 

  117. Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002;108;17–29.

    Article  CAS  PubMed  Google Scholar 

  118. Gleave M, Hsieh JT, Gao CA, von AC Eschenbach, Chung LW. Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res 1991;51:3753–3761.

    CAS  PubMed  Google Scholar 

  119. Yang J, Fizazi K, Peleg S, et al. Prostate cancer cells induce osteoblast differentiation through a Cbfa1-dependent pathway. Cancer Res 2001;61:5652–5659.

    CAS  PubMed  Google Scholar 

  120. De Pinieux G, Flam T, Zerbib M, et al. Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression in localized human prostatic adenocarcinoma as predictors of clinical out-come: a clinicopathological and immunohistochemical study of 43 cases. J Urol 2001;166:1924–1930.

    Article  PubMed  Google Scholar 

  121. Shirari T, Tamano S, Takahashi S, Ito N. Animal prostate carcinoma models: limited potential for vertebral metastasis. Adv Exp Med Biol 1992;324:151–158.

    CAS  PubMed  Google Scholar 

  122. Gu X, Shin BH, Akbarali Y, Weiss A, Boltax J, Oettgen P, Libermann TA. Tel-2 is a novel transcriptional repressor related to the Ets factor Tel/ETV-6. J Biol Chem 2001;276:9421–9436.

    Article  CAS  PubMed  Google Scholar 

  123. Tamada H, Kitazawa R, Gohji K, Kamidono S, Maeda S, Kitazawa S. Molecular cloning and analysis of the 5′-flanking region of the human bone morphogenetic protein-6 (BMP-6). Biochim Biophys Acta 1998;1395:247–251.

    CAS  PubMed  Google Scholar 

  124. Rana A, Chisholm GD, Khan M, Sekharjit SS, Merrick MV, Elton RA. Patterns of bone metastasis and their prognostic significance in patients with carcinoma of the prostate. Br J Urol 1993;72:933–936.

    Article  CAS  PubMed  Google Scholar 

  125. Bubendorf L, Schopfer A, Wagner U, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 2000;31:578–583.

    Article  CAS  PubMed  Google Scholar 

  126. Masuda H, Fukabori Y, Nakano K, Takezawa Y. TCS, Yamanaka H. Increased expression of bone morphogenetic protien-7 in bone metastatic prostate cancer. Prostate 2003;54:268–274.

    Article  CAS  PubMed  Google Scholar 

  127. Miyazaki H, Watabe T, Kitamura T, Miyazono K. BMP signals inhibit proliferation and in vivo tumor growth of androgen-insensitive prostate carcinoma cells. Oncogene 2004;23:9326–9335.

    Article  CAS  PubMed  Google Scholar 

  128. Yang S, Zhong C, Frenkel B, Reddi AH, Roy-Burman P. Diverse biological effect and Smad signaling of bone morphogenetic protein 7 in prostate tumor cells. Cancer Res 2005;65:5769–5777.

    Article  CAS  PubMed  Google Scholar 

  129. Karan D, Chen SJ, Johansson SL, et al. Dysregulated expression of MIC-1/PDF in human prostate tumor cells. Biochem Biophys Res Commun 2003;305:598–604.

    Article  CAS  PubMed  Google Scholar 

  130. Liu T, Bauskin AR, Zaunders J, et al. Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res 2003;63:5034–5040.

    CAS  PubMed  Google Scholar 

  131. Wiklund F, Gillanders EM, Albertus JA, et al. Genome-wide scan of Swedish families with hereditary prostate cancer: suggestive evidence of linkage at 5q11.2 and 19p13.3. Prostate 2003;57:290–297.

    Article  CAS  PubMed  Google Scholar 

  132. Hsieh CL, Oakley-Girvan I, Balise RR, et al. A genome screen of families with multiple cases of prostate cancer: evidence of genetic heterogeneity. Am J Hum Genet 2001;69:148–158.

    Article  CAS  PubMed  Google Scholar 

  133. Taoka R, Tsukuda F, Ishikawa M, Haba R, Kakehi Y. Association of prostatic inflammation with down-regulation of macrophage inhibitory cytokine-1 gene in symptomatic benign prostatic hyperplasia. J Urol 2004;171:2330–2335.

    Article  CAS  PubMed  Google Scholar 

  134. Nakamura T, Scorilas A, Stephan C, et al. Quantitative analysis of macrophage inhibitory cytokine-1 (MIC-1) gene expression in human prostatic tissues. Br J Cancer 2003;88:1101–1104.

    Article  CAS  PubMed  Google Scholar 

  135. Welsh JB, Sapinoso LM, Su AI, et al. Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res 2001;61:5974–5978.

    CAS  PubMed  Google Scholar 

  136. Welsh JB, Sapinoso LM, Kern SG, et al. Large-scale delineation of secreted protein biomarkers over-expressed in cancer tissue and serum. Proc Natl Acad Sci USA 2003;100:3410–3415.

    Article  CAS  PubMed  Google Scholar 

  137. Kim IY, Lee DH, Ahn HJ, et al. Expression of bone morphogenetic protein receptors type-IA,-IB and-II correltes with tumor grade in human prostate cancer tissues. Cancer Res 2000;60:2840–2844.

    CAS  PubMed  Google Scholar 

  138. Ide H, Yoshida T, Matsumoto N, et al. Growth regulation of human prostate cancer cells by bone morphogenetic protein-2. Cancer Res 1997;57:5022–5027.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA

    Tetsu Hayashida MD & Shyamala Maheswaran PhD

  2. Department of Medicine, Genetics Program and Cancer Center, Boston University School of Medicine, Boston, MA, USA

    Vandana Gupta PhD & Sam Thiagalingam PhD

Authors
  1. Tetsu Hayashida MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vandana Gupta PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sam Thiagalingam PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shyamala Maheswaran PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press

About this chapter

Cite this chapter

Hayashida, T., Gupta, V., Thiagalingam, S., Maheswaran, S. (2008). Activins, Inhibins, and Bone Morphogenetic Proteins as Modulators and Biomarkers of Prostate Cancer Progression. In: Transforming Growth Factor-β in Cancer Therapy, Volume I. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-292-2_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-292-2_22

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-714-3

  • Online ISBN: 978-1-59745-292-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation