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Published on: October 27, 2020

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

A Evangelou1, S K Jindal, T J Brown

  • 1Blood & Cancer Research Program, The Hospital for Sick Children, Toronto, Ontario, Canada.

Cancer Research
|March 8, 2000
PubMed

Insights

Androgens like DHT may promote ovarian cancer by reducing TGF-beta receptors, enabling cancer cells to evade growth inhibition. This research investigates steroid hormone regulation of TGF-beta signaling in ovarian cancer progression.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Steroid hormones are linked to epithelial ovarian cancer development and progression.
  • Ovarian surface epithelial cells exhibit growth inhibition in response to transforming growth factor beta (TGF-beta).

Purpose of the Study:

  • To investigate whether steroid hormones regulate the expression of TGF-beta1 or its receptors in ovarian cancer cells.
  • To explore the role of androgens in modulating TGF-beta signaling pathways relevant to ovarian cancer.

Main Methods:

  • Quantitative reverse transcription-PCR was used to assess mRNA expression levels of TGF-beta receptors and related molecules.
  • Western blot analysis and saturation binding assays were employed to confirm androgen receptor (AR) protein expression.
  • Ovarian cancer cell lines (HEY, OVCAR-3, SKOV-3) and primary cultures were treated with 5alpha-dihydrotestosterone (DHT) and hydroxyflutamide.

Main Results:

  • 5alpha-dihydrotestosterone (DHT) down-regulated mRNA expression of TGF-beta receptors I and II (TbetaR-I, TbetaR-II), betaglycan, and endoglin in HEY cells, without affecting TGF-beta1 mRNA.
  • Androgen receptor (AR) expression varied significantly across cell lines, with HEY and SKOV-3 cells showing very low levels.
  • DHT treatment dose-dependently down-regulated TbetaR-II mRNA in SKOV-3 and HEY cells, and reversed TGF-beta1-induced growth inhibition.
  • The AR antagonist hydroxyflutamide exhibited androgen-mimetic activity, down-regulating TbetaR-II mRNA in SKOV-3 cells.

Conclusions:

  • Androgens may contribute to ovarian cancer progression by reducing TGF-beta receptor expression, thus diminishing TGF-beta1-mediated growth inhibition.
  • The observed effects may be influenced by AR co-activators like AR-associating protein 70 in certain ovarian cancer cell lines.
  • These findings highlight a potential mechanism by which steroid hormones impact ovarian cancer cell behavior and suggest therapeutic targets.

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