Advertisement

Ovarian Cancer pp 293-302 | Cite as

Role of Inhibins and Activins in Ovarian Cancer

  • Teresa K. Woodruff
Part of the Cancer Treatment and Research book series (CTAR, volume 107)

Abstract

Ovarian cancer strikes 1 in 70 women and is usually fatal. The frank mortality associated with this disease is largely due to the lack of effective diagnostics and a poor understanding of the molecular basis of the disease. Few factors have been directly correlated with the tissue-specific onset of cancer, however, recent work on inhibins and activins may provide clues to ovarian cancer onset and progression.

Keywords

Ovarian Cancer Granulosa Cell Follicle Stimulate Hormone Granulosa Cell Tumor Activin Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Woodruff TK Regulation of Cellular and System Function by Activin. Biochemical Pharmacology 1997; 55: 953–963.Google Scholar
  2. 2.
    Vale W, Rivier C, Hsueh A, Campen C, Meunier H, and Bicsak T. Chemical and biological characterization of the inhibin family of protein hormones. Recent Progress in Hormone Research 1988; 44: 1–34.PubMedGoogle Scholar
  3. 3.
    Woodruff, T., D’Agostino, J., Schwartz, N., Mayo, K. Dynamic changes in inhibin messenger RNAs in rat ovarian follicles during the reproductive cycle. Science 1988; 239: 1296–1299.PubMedCrossRefGoogle Scholar
  4. 4.
    Woodruff, T., Mather, J. Inhibin, activin and the female reproductive axis. Ann Rev Physiol 1995; 57: 219–244.CrossRefGoogle Scholar
  5. 5.
    Woodruff, T.K., Lyon, R.J., Hansen, S.E., Rice, G.C., Mather, J.P. Inhibin and activin locally regulate rat ovarian folliculogenesis. Endocrinology. 1990; 127: 3196–3205.PubMedCrossRefGoogle Scholar
  6. 6.
    Hillier, S., Yong, E., Illingworth, P., Baird, D., Schwall, R., Mason, A. Effect of recombinant inhibin on androgen synthesis in cultured human thecal cells. Mol Cell Endocrinol 1991; 75: R1 - R6.PubMedCrossRefGoogle Scholar
  7. 7.
    Stouffer, R.L., Dahl, K.D., Hess, D.L., Woodruff, T.K., Mather, J.P., Molkness, T.A. Systemic and intraluteal infusion of inhibin A and activin A in rhesus monkeys during the luteal phase of the menstrual cycle. Biol Reprod 1994; 50: 888–895.PubMedCrossRefGoogle Scholar
  8. 8.
    Molskness, T., Woodruff, T.K., Hess, D., Dahl, K., Stouffer, D. Recombinant human inhibin A administered early in the menstrual cycle alters concurrent pituitary and follicular, plus subsequent luteal, function in rhesus monkeys. J Clin Endocrinol Met 1996; 81: 4002–4006.CrossRefGoogle Scholar
  9. 9.
    Massague, J. TGF signaling: receptors, transducers, and MAD proteins. Cell 1996; 85: 947–950.PubMedCrossRefGoogle Scholar
  10. 10.
    Massague J, Cheifetz S, Laiho M, Ralph D, Weis F, and Zentella A. Transforming growth factor-beta. Cancer Surveys. 1992; 12: 81–103.PubMedGoogle Scholar
  11. 11.
    Mathews, L. Activin receptors and cellular signaling by the receptor serine kinase family. Endocrine Reviews: 1994; 15: 310–325.PubMedGoogle Scholar
  12. 12.
    Mathews, L.S., Vale, W.W. Expression cloning of an activin receptor, a predicted transmembrane serine kinase. Cell 1991; 65: 973–982.PubMedCrossRefGoogle Scholar
  13. 13.
    Attisano, L., Wrana, J., Cheifetz, S., Massague, J. Novel activin receptors: Distinct genes and alternative mRNA splicing generate a repertoire of serine threonine kinase receptors. Cell 1992; 86: 97–108.CrossRefGoogle Scholar
  14. 14.
    Sekelsky J, Newfeld S, Raftery L, Chartoff E, and Gelbart W. Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 1995; 139: 1347–1358.PubMedGoogle Scholar
  15. 15.
    Graff J, Bansal A, and Melton D. Xenopus Mad proteins transduce distinct subsets of signals for the TGFB superfamily. Cell 1996; 85: 479–487.PubMedCrossRefGoogle Scholar
  16. 16.
    Derynck R, Gelbart WM, Harland RM, Heldin CH, Kern SE, Massague J, Melton DA, Mlodzik M, Padgett RW, Roberts AB, Smith J, Thomsen GH, Vogelstein B, and Wang XF. Nomenclature: vertebrate mediators of TGFbeta family signals. Cell 1996; 87: 173175.Google Scholar
  17. 17.
    Hoodless P, Haerry T, Abdollah S, Stapleton M, O’Connor M, Attisano L, and Wrana J. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell 196; 85: 489–500.Google Scholar
  18. 18.
    Liu F, Hata A, Baker J, Doody J, Carcamo J, Harland R, and Massague J. A human Mad protein activin as a BMP-regulated transcriptional activator. Nature 1996; 381: 620–623.PubMedCrossRefGoogle Scholar
  19. 19.
    Lagna G, Hata A, Hemmati-Brivanlou A, and Massague J. Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways. Nature 1996; 383: 832–836.PubMedCrossRefGoogle Scholar
  20. 20.
    Eppert K, Scherer S, Ozcelik J, Perone R, Hoodless P, Kim H, Tsui L, Bapat B, Gallinger S, Andrulis I, Thomsen G, Wrana J, and Attisano L. Madr2 maps to 18g21 and encodes a TGFb-regulated MAD-related protein that is functionally mutated in colorectoal carcinoma. Cell 1996; 86: 543–552.PubMedCrossRefGoogle Scholar
  21. 21.
    Macias-Silva M, Abdollah S, Hoodless PA, Pirone R, Attisano L, and Wrana JL. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell 1996; 87: 1215–24.PubMedCrossRefGoogle Scholar
  22. 22.
    Wu T-Y, Zhang Y, Feng X, and Derynck R. Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of smad3 and smad4/dpc4. Molecular and Cellular Biology 1997; 17: 2521–2528.PubMedGoogle Scholar
  23. 23.
    Hahn SA, Schutte M, Hogue AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, and Kern SE. DPC4, a candidate tumor suppressor gene at human chromosome 18g21.1. Science 1996; 271: 350–353.PubMedCrossRefGoogle Scholar
  24. 24.
    Schutte M, Hruban RH, Hedrick L, Cho KR, Nadasdy GM, Weinstein CL, Bova GS, Isaacs WB, Cairns P, Nawroz H, Sidransky D, Casero RA Jr, Meltzer PS, Hahn SA, and Kern S. DPC4 gene in various tumor types. Cancer Research 1996; 56: 2527–2530.PubMedGoogle Scholar
  25. 25.
    Yingling JM, Das P, Savage C, Zhang M, Padgett RW, Wang XF. Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth. Proceedings of the National Academy of Sciences of the United States of America 1996; 93: 8940–8944.PubMedCrossRefGoogle Scholar
  26. 26.
    Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW, and Vogelstein B. Mad-related genes in the human. Nature Genetics 1996; 13: 347–349.PubMedCrossRefGoogle Scholar
  27. 27.
    Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, Miyazono K. Smad6 inhibits signalling by the TGF-beta superfamily. Nature 1997; 389: 622–626.PubMedCrossRefGoogle Scholar
  28. 28.
    Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke P. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 1997; 389: 631–635.PubMedCrossRefGoogle Scholar
  29. 29.
    Shi Y, Hata A, Lo RS, Massague J, Pavletich NP. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature 1997; 388: 87–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Hata A, Lo RS, Wotton D, Lagna G, Massague J. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature 1997; 388: 82–87.PubMedCrossRefGoogle Scholar
  31. 31.
    Kalkhoven E, Roelen BA, de Winter JP, Mummery CL, van den Eijnden-van Raaij AJ, van der Saag PT, and van der Burg B. Resistance to transforming growth factor beta and activin due to reduced receptor expression in human breast tumor cell lines. Cell Growth & Differentiation 1995; 6: 1151–1161.Google Scholar
  32. 32.
    Matzuk MM, Kumar TR, Shou W, Coerver KA, Lau AL, Behringer RR, and Finegold MJ. Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development. Recent Progress in Hormone Research 1996; 51: 123–154.PubMedGoogle Scholar
  33. 33.
    Blaustein A. Surface germinal epithelium and related ovarian neoplasms. Pathology Annuals 1981; 16: 247–294.Google Scholar
  34. 34.
    Coerver, K, Woodruff, TK, Finegold, M, Mather, J, Bradley, A, Matzuk, M. Molec Endocrinol 1996; 10: 534–538.CrossRefGoogle Scholar
  35. 35.
    Groome NP, Illingworth PI, O’Brien M, Pai R, Rodger FE, Mather JP, and McNeilly AS. J Clin Endocrinol Metabol 1996; 81: 1401–1405.CrossRefGoogle Scholar
  36. 36.
    Healy, D, Burger, H, Mamers, P, Jobling, T, Bangah, M, Quinn, M. New Eng J Med 1996; 329: 1539–1342.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Teresa K. Woodruff
    • 1
  1. 1.Department of Neurobiology and Physiology, Northwestern University and Department of MedicineNorthwestern University Medical SchoolEvanstonUSA

Personalised recommendations