Regulation of Akt/PKB activity, cellular growth, and apoptosis in prostate carcinoma cells by MMAC/PTEN

Michael A. Davies, Dimpy Koul, Haninder Dhesi, Russell Berman, Timothy J. McDonnell, David McConkey, W. K.Alfred Yung, Peter A. Steck

Research output: Contribution to journalArticle

Abstract

Understanding the functional roles of the molecular alterations that are involved in the oncogenesis of prostate cancer, the second most frequent cause of cancer-related deaths among men in the United States is the focus of numerous investigations. To examine the possible significance of alterations associated with the tumor suppressor gene, MMAC/PTEN, in prostate carcinoma, the biological and biochemical effects of MMAC/PTEN expression were examined in LNCaP cells, which are devoid of a functional gene product. Acute expression of MMAC/PTEN via an adenoviral construct resulted in a dose- dependent and specific inhibition of Akt/PKB activation, consistent with the phosphatidylinositol phosphatase activity of MMAC/PTEN. MMAC/PTEN expression induced apoptosis in LNCaP cells, although to a lesser extent than that observed with p53 via an adenoviral construct. However, MMAC/PTEN expression produced a growth inhibition that was significantly greater than that achieved with p53. Overexpression of Bcl-2 in LNCaP cells blocked MMAC/PTEN- and p53-induced apoptosis but not the growth-suppressive effects of MMAC/PTEN, suggesting that the growth regulatory effects of MMAC/PTEN involve multiple pathways. These studies further implicate the loss of MMAC/PTEN as a significant event in prostate cancer and suggest that reintroduction of MMAC/PTEN into deficient prostate cancer cells may have therapeutic implications.

Original languageEnglish (US)
Pages (from-to)2551-2556
Number of pages6
JournalCancer Research
Volume59
Issue number11
StatePublished - Jun 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Davies, M. A., Koul, D., Dhesi, H., Berman, R., McDonnell, T. J., McConkey, D., Yung, W. K. A., & Steck, P. A. (1999). Regulation of Akt/PKB activity, cellular growth, and apoptosis in prostate carcinoma cells by MMAC/PTEN. Cancer Research, 59(11), 2551-2556.