Down-regulation of transforming growth factor β receptors by androgen in ovarian cancer cells

Andreas Evangelou, Sangita K. Jindal, Theodore J. Brown, Michelle Letarte

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Steroid hormones have been implicated in the etiology and/or progression of epithelial ovarian cancer. As ovarian surface epithelial cells are growth inhibited by transforming growth factor β (TGF-β), we tested whether steroid hormones could regulate the expression of TGF-β1 or its receptors in ovarian cancer cells, as assessed by quantitative reverse transcription-PCR. Treatment of ovarian cancer HEY cells with 500 nM 5α-dihydrotestosterone (DHT), but not estradiol-17β or progesterone, for 60 h down-regulated the expression of mRNA for TGF-β receptors I and II (TβR-I and TβR-II), betaglycan, and endoglin but had no effect on TGF-β1 mRNA levels. Androgen receptor (AR) mRNA expression in HEY cells was compared to other ovarian cancer cell lines. OVCAR-3 cells expressed AR mRNA levels similar to that of androgen-responsive LNCaP prostate cancer cells, whereas SKOV-3 and HEY cells expressed only 3 and 0.01%, respectively. Western blot analysis and saturation binding assays confirmed the expression of AR protein in these three cell lines, but at the limit of detection in SKOV-3 and HEY cells. Treatment of SKOV-3 and HEY cells for 24 h with 1-50 nM DHT resulted in a dose-dependent down-regulation of TβR-II mRNA. The AR antagonist hydroxyflutamide did not reverse the effect of DHT on SKOV-3 cells but by itself downregulated TβR-II mRNA. This apparent androgen-mimetic action of hydroxyflutamide and the ability of SKOV-3 and HEY cells to respond to DHT may be due to their expression of AR-associating protein 70, an AR co- activator reported to amplify AR transactivation and to result in agonist activity of AR antagonists. DHT was able to reverse TGF-β1 growth-inhibitory action in SKOV-3 cells and in a primary culture of ovarian cancer cells derived from ascites. Thus, androgens may promote ovarian cancer progression in part by decreasing TGF-β receptor levels, thereby allowing ovarian cancer cells to escape TGF-β1 growth inhibition.

Original languageEnglish (US)
Pages (from-to)929-935
Number of pages7
JournalCancer Research
Volume60
Issue number4
StatePublished - Feb 15 2000
Externally publishedYes

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Ovarian Neoplasms
Androgens
Down-Regulation
Androgen Receptors
Dihydrotestosterone
Messenger RNA
Androgen Receptor Antagonists
Growth
Steroids
Hormones
Cell Line
Ascites
Transcriptional Activation
Reverse Transcription
Progesterone
Limit of Detection
Estradiol
Prostatic Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Down-regulation of transforming growth factor β receptors by androgen in ovarian cancer cells. / Evangelou, Andreas; Jindal, Sangita K.; Brown, Theodore J.; Letarte, Michelle.

In: Cancer Research, Vol. 60, No. 4, 15.02.2000, p. 929-935.

Research output: Contribution to journalArticle

Evangelou, Andreas ; Jindal, Sangita K. ; Brown, Theodore J. ; Letarte, Michelle. / Down-regulation of transforming growth factor β receptors by androgen in ovarian cancer cells. In: Cancer Research. 2000 ; Vol. 60, No. 4. pp. 929-935.
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