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[Cancer Research 59, 2551-2556, June 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 2551-2556, June 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Regulation of Akt/PKB Activity, Cellular Growth, and Apoptosis in Prostate Carcinoma Cells by MMAC/PTEN1

Michael A. Davies, Dimpy Koul, Haninder Dhesi, Russell Berman, Timothy J. McDonnell, David McConkey, W. K. Alfred Yung and Peter A. Steck2

Departments of Neuro-Oncology [M. A. D., D. K., H. D., W. K. A. Y., P. A. S.], Molecular Pathology [T. J. M.], and Cell Biology [R. B., D. M.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

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.




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