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Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)

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Abstract

Cyclooxygenase (COX) (PTGS) is the rate-limiting enzyme in the biosynthesis of prostaglandins. Two COX isoforms have been identified, COX-1 and COX-2, which show distinct cell-specific expression and regulation. Ovarian cancer is the most lethal gynecological malignancy and the disease is poorly understood due to the lack of suitable animal models. The laying hen spontaneously develops epithelial ovarian cancer with few or no symptoms until the cancer has progresses to a late stage, similar to the human disease. The purpose of this study was to examine the relative expression and distribution of COX-1 and COX-2 in the ovaries of normal hens and in hens with ovarian cancer. The results demonstrate that COX-1 was localized to the granulosa cell layer and cortical interstitium, ovarian surface epithelium (OSE) and postovulatory follicle (POF) of the normal ovary. In ovarian cancer, COX-1 mRNA was significantly increased and COX-1 protein was broadly distributed throughout the tumor stroma. COX-2 protein was localized to the granulosa cell layer in the follicle and the ovarian stroma. COX-2 mRNA expression did not change as a function of age or in ovarian cancer. There was significantly higher expression of COX-1 mRNA in the first POF (POF-1) compared to POF-2 and POF-3. COX-2 mRNA expression was not significantly different among POFs. There was no difference in COX-1 or COX-2 mRNA in the OSE isolated from individual follicles in the follicular hierarchy. The results confirm previous findings of the high expression of COX-1 in ovarian tumors further supporting the laying hen as a model for ovarian cancer, and demonstrate for the first time the high expression of COX-1 in POF-1 which is the source of prostaglandins needed for oviposition.

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References

  1. UCSW Group, United States Cancer Statistics: 2002 Incidence and Mortality. (US Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute, 2005)

  2. T.N. Fredrickson, Ovarian tumors of the hen. Environ. Health Perspect. 73, 35–51 (1987)

    Article  CAS  PubMed  Google Scholar 

  3. C. Rodriguez-Burford, M.N. Barnes, W. Berry, E.E. Partridge, W.E. Grizzle, Immunohistochemical expression of molecular markers in an avian model: a potential model for preclinical evaluation of agents for ovarian cancer chemoprevention. Gynecol. Oncol. 81, 373–379 (2001)

    Article  CAS  PubMed  Google Scholar 

  4. J.R. Giles, H.L. Shivaprasad, P.A. Johnson, Ovarian tumor expression of an oviductal protein in the hen: a model for human serous ovarian adenocarcinoma. Gynecol. Oncol. 95, 530–533 (2004)

    Article  CAS  PubMed  Google Scholar 

  5. N. Auersperg, A.S. Wong, K.C. Choi, S.K. Kang, P.C. Leung, Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr. Rev. 22, 255–288 (2001)

    Google Scholar 

  6. C.H. Lingeman, Etiology of cancer of the human ovary: a review. J. Natl. Cancer Inst. 53, 1603–1618 (1974)

    CAS  PubMed  Google Scholar 

  7. S. Mabuchi, D.A. Altomare, D.C. Connolly, A. Klein-Szanto, S. Litwin, M.K. Hoelzle, H.H. Hensley, T.C. Hamilton, J.R. Testa, RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res. 67, 2408–2413 (2007)

    Article  CAS  PubMed  Google Scholar 

  8. T. Daikoku, S. Tranguch, I.N. Trofimova, D.M. Dinulescu, T. Jacks, A.Y. Nikitin, D.C. Connolly, S.K. Dey, Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer. Cancer Res. 66, 2527–2531 (2006)

    Article  CAS  PubMed  Google Scholar 

  9. D.M. Dinulescu, T.A. Ince, B.J. Quade, S.A. Shafer, D. Crowley, T. Jacks, Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat. Med. 11, 63–70 (2005)

    Article  CAS  PubMed  Google Scholar 

  10. S.K. Bristol-Gould, C.G. Hutten, C. Sturgis, S.M. Kilen, K.E. Mayo, T.K. Woodruff, The development of a mouse model of ovarian endosalpingiosis. Endocrinology 146, 5228–5236 (2005)

    Article  CAS  PubMed  Google Scholar 

  11. D.C. Connolly, R. Bao, A.Y. Nikitin, K.C. Stephens, T.W. Poole, X. Hua, S.S. Harris, B.C. Vanderhyden, T.C. Hamilton, Female mice chimeric for expression of the simian virus 40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Res. 63, 1389–1397 (2003)

    CAS  PubMed  Google Scholar 

  12. A. Flesken-Nikitin, K.C. Choi, J.P. Eng, E.N. Shmidt, A.Y. Nikitin, Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res. 63, 3459–3463 (2003)

    CAS  PubMed  Google Scholar 

  13. R. Wu, N. Hendrix-Lucas, R. Kuick, Y. Zhai, D.R. Schwartz, A. Akyol, S. Hanash, D.E. Misek, H. Katabuchi, B.O. Williams, E.R. Fearon, K.R. Cho, Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-catenin and PI3K/Pten signaling pathways. Cancer Cell 11, 321–333 (2007)

    Article  CAS  PubMed  Google Scholar 

  14. M.F. Fathalla, Incessant ovulation—a factor in ovarian neoplasia? Lancet 2, 163 (1971)

    Article  CAS  PubMed  Google Scholar 

  15. D.A. Kujubu, B.S. Fletcher, B.C. Varnum, R.W. Lim, H.R. Herschman, TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J. Biol. Chem. 266, 12866–12872 (1991)

    CAS  PubMed  Google Scholar 

  16. C.S. Williams, M. Mann, R.N. DuBois, The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18, 7908–7916 (1999)

    Article  CAS  PubMed  Google Scholar 

  17. H.R. Herschman, J.J. Talley, R. DuBois, Cyclooxygenase 2 (COX-2) as a target for therapy and noninvasive imaging. Mol. Imaging Biol. 5, 286–303 (2003)

    Article  PubMed  Google Scholar 

  18. K. Subbaramaiah, A.J. Dannenberg, Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol. Sci. 24, 96–102 (2003)

    Article  CAS  PubMed  Google Scholar 

  19. S.M. Prescott, F.A. Fitzpatrick, Cyclooxygenase-2 and carcinogenesis. Biochim. Biophys. Acta 1470, M69–78 (2000)

    CAS  PubMed  Google Scholar 

  20. W.L. Yang, I.H. Roland, A.K. Godwin, X.X. Xu, Loss of TNF-alpha-regulated COX-2 expression in ovarian cancer cells. Oncogene 24, 7991–8002 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. R.A. Gupta, L.V. Tejada, B.J. Tong, S.K. Das, J.D. Morrow, S.K. Dey, R.N. DuBois, Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer. Cancer Res. 63, 906–911 (2003)

    CAS  PubMed  Google Scholar 

  22. T. Daikoku, D. Wang, S. Tranguch, J.D. Morrow, S. Orsulic, R.N. DuBois, S.K. Dey, Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer. Cancer Res. 65, 3735–3744 (2005)

    Article  CAS  PubMed  Google Scholar 

  23. M.E. Urick, P.A. Johnson, Cyclooxygenase 1 and 2 mRNA and protein expression in the Gallus domesticus model of ovarian cancer. Gynecol. Oncol. 103, 673–678 (2006)

    Article  CAS  PubMed  Google Scholar 

  24. S. Li, K. Miner, R. Fannin, J. Carl Barrett, B.J. Davis, Cyclooxygenase-1 and 2 in normal and malignant human ovarian epithelium. Gynecol. Oncol. 92, 622–627 (2004)

    Article  CAS  PubMed  Google Scholar 

  25. G. Lee, H.T. Ng, Clinical evaluations of a new ovarian cancer marker, COX-1. Intl. J. Gynaecol. Obstetr. Official Organ Intl. Feder. Gynaecol. Obstetr. 49(Suppl), 27–32 (1995)

    Google Scholar 

  26. Y. Kino, F. Kojima, K. Kiguchi, R. Igarashi, B. Ishizuka, S. Kawai, Prostaglandin E2 production in ovarian cancer cell lines is regulated by cyclooxygenase-1, not cyclooxygenase-2. Prostaglandins, Leukotrienes, Essential Fatty Acids 73, 103–111 (2005)

    Article  CAS  Google Scholar 

  27. J. Bahr, The avian ovary: model for endocrine studies. J. Exp. Zool. 4(Suppl), 192–194 (1990)

    Article  CAS  Google Scholar 

  28. J.M. Bahr, A.L. Johnson, Regulation of the follicular hierarchy and ovulation. J. Exp. Zool. 232, 495–500 (1984)

    Article  CAS  PubMed  Google Scholar 

  29. P.A. Johnson, J.R. Giles, Use of genetic strains of chickens in studies of ovarian cancer. Poult. Sci. 85, 246–250 (2006)

    CAS  PubMed  Google Scholar 

  30. J.R. Giles, L.M. Olson, P.A. Johnson, Characterization of ovarian surface epithelial cells from the hen: a unique model for ovarian cancer. Exp. Biol. Med. 231, 1718–1725 (2006)

    CAS  Google Scholar 

  31. B.C. Vanderhyden, T.J. Shaw, J.F. Ethier, Animal models of ovarian cancer. Reprod. Biol. Endocrinol. 67(1), 1–11 (2003)

    Google Scholar 

  32. M.N. Barnes, W.D. Berry, J.M. Straughn, T.O. Kirby, C.A. Leath, W.K. Huh, W.E. Grizzle, E.E. Partridge, A pilot study of ovarian cancer chemoprevention using medroxyprogesterone acetate in an avian model of spontaneous ovarian carcinogenesis. Gynecol. Oncol. 87, 57–63 (2002)

    Article  CAS  PubMed  Google Scholar 

  33. W.J. Murdoch, J.F. Martinchick, Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: carcinogenic implication and chemoprevention. Exp. Biol. Med. (Maywood) 229, 546–552 (2004)

    CAS  Google Scholar 

  34. W.J. Murdoch, E.A. Van Kirk, B.M. Alexander, DNA damages in ovarian surface epithelial cells of ovulatory hens. Exp. Biol. Med. (Maywood) 230, 429–433 (2005)

    CAS  Google Scholar 

  35. W.J. Murdoch, R.S. Townsend, A.C. McDonnel, Ovulation-induced DNA damage in ovarian surface epithelial cells of ewes: prospective regulatory mechanisms of repair/survival and apoptosis. Biol. Reprod. 65, 1417–1424 (2001)

    Article  CAS  PubMed  Google Scholar 

  36. W.J. Murdoch, A.C. McDonnel, Roles of the ovarian surface epithelium in ovulation and carcinogenesis. Reproduction 123, 743–750 (2001)

    Article  Google Scholar 

  37. T.D. Oberley, Oxidative damage and cancer. Am. J. Pathol. 160, 403–408 (2001)

    Google Scholar 

  38. L.M. Coussens, Z. Werb, Inflammation and cancer. Nature 420, 860–867 (2002)

    Article  CAS  PubMed  Google Scholar 

  39. I. Rothchild, R.M. Fraps, On the function of the ruptured ovarian follicle of the domestic fowl. Proc Soc Exp Biol Med N.Y. 56, 79–82 (1944)

    Google Scholar 

  40. J. Bahr, P. Johnson, Reproduction in poulty, in Reproduction in Domestic Animals, ed. P. Cupps (Academic Press, New York, 1991), pp. 555–575

  41. W.Y. Wong, J.S. Richards, Evidence for two antigenically distinct molecular weight variants of prostaglandin H synthase in the rat ovary. Mol. Endocrinol. 5, 1269–1279 (1991)

    Article  CAS  PubMed  Google Scholar 

  42. A. Hayes, T. Scase, J. Miller, S. Murphy, A. Sparkes, V. Adams, COX-1 and COX-2 expression in feline oral squamous cell carcinoma. J. Comparat. Pathol. 135, 93–99 (2006)

    Article  CAS  Google Scholar 

  43. J.S. Richards, D.L. Russell, S. Ochsner, L.L. Espey, Ovulation: new dimensions and new regulators of the inflammatory-like response. Annu. Rev. Physiol. 64, 69–92 (2002)

    Article  CAS  PubMed  Google Scholar 

  44. U.R. Mbonye, M. Wada, C.J. Rieke, H.-Y. Tang, D.L. DeWitt, W.L. Smith, The 19-amino acid cassette of cyclooxygenase-2 mediates entry of the protein into the endoplasmic reticulum-associated degradation system. J. Biol. Chem. 281, 35770–35778 (2006)

    Google Scholar 

  45. M. Wada, C.J. Delong, Y.H. Hong, C.J. Rieke, I. Song, R.S. Sidhu, C. Yuan, M. Warnock, A.H. Schmaier, C. Yokoyama, E.M. Smyth, S.J. Wilson, G.A. Fitzgerald, R.M. Garavito, D.X. Sui, J.W. Regan, W.L. Smith, Enzymes and receptors of prostaglandin pathways with arachidonic acid- vs. eicosapentaenoic acid-derived substrates and products. J. Biol. Chem. 282, 22254–22266 (2007)

    Google Scholar 

  46. G. Gomori, A rapid one-step trichrome stain. Am. J. Clin. Pathol. 20, 661–664 (1950)

    CAS  PubMed  Google Scholar 

  47. D.C. Skeehan, B.B. Hrapchak, Theory and practice of histological techniques (Mosby, St. Louis, 1973), pp. 111–112

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Acknowledgments

This work was funded by Department of Defense, Ovarian Cancer Research Program, OC050091 (DBH); American Institute for Cancer Research, 06-A043 (DBH). We are grateful for the expert histological support from Patty Mavrogianis and Lindsay Yorke-Gallagher; expert technical support from Angela Dirks; and poultry management by Chet Utterback, Douglas Hilgendorf, and Pam Utterback.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Illinois College of Medicine at Chicago, 835 S Wolcott Ave, Chicago, IL, 60612-7342, USA

    Dale Buchanan Hales, Yan Zhuge, Jo Ann Jaen Lagman, Kristine Ansenberger & Cassandra Mahon

  2. Department of Pharmacology, Rush University Medical School, 1735 W Harrison, Chicago, IL, 60612, USA

    Animesh Barua & Judith L. Luborsky

  3. Department of Animal Sciences, University of Illinois Urbana-Champaign, 1207 W. Gregory Dr, Urbana, IL, 61801, USA

    Janice M. Bahr

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  1. Dale Buchanan Hales
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Correspondence to Dale Buchanan Hales.

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Hales, D.B., Zhuge, Y., Lagman, J.A.J. et al. Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus). Endocr 33, 235–244 (2008). https://doi.org/10.1007/s12020-008-9080-z

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  • DOI: https://doi.org/10.1007/s12020-008-9080-z

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