Effect of reproductive hormones on ovarian epithelial tumors

I. Effect on cell cycle activity

Hong Zhou, Michelle Ping Luo, Axel H. Schönthal, Malcolm C. Pike, Michael R. Stallcup, Martina Blumenthal, Wenxin Zheng, Louis Dubeau

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We examined the effects of the 4 major female reproductive hormones, estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), and luteinizing hormone (LH) on thymidine incorporation in benign and malignant ovarian epithelial tumors cultured in vitro. Treatment of these tumors with E2, FSH and LH resulted in increased thymidine incorporation while treatment with P4 inhibited growth as well as thymidine incorporation. The inhibitory effect of progesterone could not be reproduced by treating the cells with ligands for other steroid hormone receptors known to interact with P4 such as the mineralocorticoid and glucocorticoid receptors. All cells lines expressed at least the PR-A isoform of the progesterone receptor. ORG2058, R5020, RU486, and ZK98299 acted as progesterone receptor agonists with regard to their effect on thymidine incorporation. P4 down-regulated cyclin B1 expression and cdk1 activity and up-regulated the p21 and p27 proteins. Expression of a reporter gene downstream to an AP-1 responsive element in a plasmid construct transfected into ovarian epithelial tumor cells was induced by P4 and inhibited by RU486. We conclude that P4 inhibits cell cycle activity in ovarian epithelial tumors, in part via down-regulation of the cdk1/cyclin B complex. This inhibitory effect may have therapeutic utility against ovarian epithelial tumors.

Original languageEnglish (US)
Pages (from-to)300-306
Number of pages7
JournalCancer Biology and Therapy
Volume1
Issue number3
StatePublished - May 1 2002

Fingerprint

Thymidine
Cell Cycle
Hormones
Follicle Stimulating Hormone
Progesterone Receptors
Luteinizing Hormone
Progesterone
Neoplasms
Promegestone
Cyclin B
Cyclin B1
Mineralocorticoid Receptors
Steroid Receptors
Glucocorticoid Receptors
Transcription Factor AP-1
Reporter Genes
Estradiol
Protein Isoforms
Plasmids
Down-Regulation

Keywords

  • Cell cycle
  • Gonadotropin hormones
  • Ovarian cancer
  • Steroid hormones

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Zhou, H., Luo, M. P., Schönthal, A. H., Pike, M. C., Stallcup, M. R., Blumenthal, M., ... Dubeau, L. (2002). Effect of reproductive hormones on ovarian epithelial tumors: I. Effect on cell cycle activity. Cancer Biology and Therapy, 1(3), 300-306.

Effect of reproductive hormones on ovarian epithelial tumors : I. Effect on cell cycle activity. / Zhou, Hong; Luo, Michelle Ping; Schönthal, Axel H.; Pike, Malcolm C.; Stallcup, Michael R.; Blumenthal, Martina; Zheng, Wenxin; Dubeau, Louis.

In: Cancer Biology and Therapy, Vol. 1, No. 3, 01.05.2002, p. 300-306.

Research output: Contribution to journalArticle

Zhou, H, Luo, MP, Schönthal, AH, Pike, MC, Stallcup, MR, Blumenthal, M, Zheng, W & Dubeau, L 2002, 'Effect of reproductive hormones on ovarian epithelial tumors: I. Effect on cell cycle activity', Cancer Biology and Therapy, vol. 1, no. 3, pp. 300-306.
Zhou H, Luo MP, Schönthal AH, Pike MC, Stallcup MR, Blumenthal M et al. Effect of reproductive hormones on ovarian epithelial tumors: I. Effect on cell cycle activity. Cancer Biology and Therapy. 2002 May 1;1(3):300-306.
Zhou, Hong ; Luo, Michelle Ping ; Schönthal, Axel H. ; Pike, Malcolm C. ; Stallcup, Michael R. ; Blumenthal, Martina ; Zheng, Wenxin ; Dubeau, Louis. / Effect of reproductive hormones on ovarian epithelial tumors : I. Effect on cell cycle activity. In: Cancer Biology and Therapy. 2002 ; Vol. 1, No. 3. pp. 300-306.
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