Regulation of Bcl-2 during androgen-unresponsive progression of prostate cancer

C. A. Rothermund, D. Kondrikov, M. F. Lin, J. K. Vishwanatha

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The progression of prostate cancer from androgen-responsive to an androgen-unresponsive state remains the greatest obstacle in the treatment of this disease. Androgen-unresponsive prostate cancer is highly resistant to chemotherapy and radiation treatment that kill cells by the induction of apoptosis. Elucidating the molecular mechanisms of apoptosis regulation in prostate cancer can be useful in the development of new strategies for effective therapy of androgen-unresponsive cancer. We analyzed the Bcl-2 family of apoptosis regulators using various passages of the LNCaP prostate cancer cell line, which serve as an in vitro model for the progression of prostate cancer from androgen-responsive to androgen-unresponsive. In our model, progressively higher passages of LNCaP cells represent the progression to androgen-unresponsiveness. We examined the basal mRNA expression of the Bcl-2 family of apoptosis regulators. Under normal growth conditions, both androgen-responsive and androgen-unresponsive LNCaP cells express the Bcl-2 family of genes at similar levels. Western blot analysis showed the presence of Bcl-2 protein in androgen-responsive cells but not in androgen-unresponsive cells. Both androgen-responsive and androgen-unresponsive cells expressed Bax protein at similar levels. When exposed to oxidative stress, androgen-responsive cells underwent apoptosis but androgen-unresponsive cells exhibited resistance suggesting that the progression to androgen-unresponsiveness was associated with altered regulation of apoptosis. Treatment with paclitaxel or sodium butyrate induced apoptosis in both androgen-responsive and androgen-unresponsive cells suggesting that the apoptotic machinery is still intact in androgen-unresponsive LNCaP cells.

Original languageEnglish (US)
Pages (from-to)236-245
Number of pages10
JournalProstate Cancer and Prostatic Diseases
Volume5
Issue number3
DOIs
StatePublished - Oct 19 2002

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Keywords

  • Androgen-unresponsive
  • Apoptosis
  • Bcl-2
  • LNCaP
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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