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Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module
10:39

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Published on: June 18, 2015

CDB-4124, a progesterone receptor modulator, inhibits mammary carcinogenesis by suppressing cell proliferation and

Ronald Wiehle1, Daniel Lantvit, Tohru Yamada

  • 1Repros Therapeutics, Inc., The Woodlands, TX 77380, USA. rwiehle@reprosrx.com

Cancer Prevention Research (Philadelphia, Pa.)
|December 2, 2010
PubMed

Insights

CDB-4124, a progesterone receptor modulator, prevents mammary lesions and suppresses carcinogen-induced mammary tumors in rats. This suggests potential for breast cancer prevention and treatment.

Area of Science:

  • Endocrinology
  • Oncology
  • Cell Biology

Background:

  • CDB-4124 (telapristone acetate) is a progesterone receptor (PR) modulator.
  • It is investigated for breast cancer prevention and treatment, and has been used for uterine fibroids and endometriosis.

Purpose of the Study:

  • To investigate CDB-4124's effects on steroid hormone signaling, cell cycle genes, and mammary carcinogenesis in vivo.
  • To evaluate its potential for breast cancer prevention and treatment.

Main Methods:

  • Rats were administered CDB-4124 orally for 24 months or via subcutaneous pellets to suppress N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis.
  • Effects on tumor latency, incidence, multiplicity, and burden were assessed.
  • Cell proliferation, apoptosis, PR, ER, and serum hormone levels were analyzed.
  • Mechanistic studies were performed in T47D cells.

Main Results:

  • CDB-4124 prevented spontaneous mammary lesions and dose-dependently suppressed MNU-induced mammary carcinogenesis.
  • It increased tumor latency, decreased incidence and multiplicity, and reduced tumor burden.
  • CDB-4124 inhibited cell proliferation and induced apoptosis in tumors, correlating with decreased PR(+) cells and serum progesterone.
  • It suppressed G(1)/G(0)-S transition by inhibiting CDK2 and CDK4, correlating with ER expression inhibition.

Conclusions:

  • CDB-4124 suppresses precancerous mammary lesions and carcinogen-induced ER(+) mammary tumors in rats.
  • These findings support its potential role in the prevention and treatment of human breast cancer.

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