Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells

Purpose: The purpose of this study was to determine the effects of adenoviral transgene expression of MMAC/PTEN on the in vitro and in vivo growth and survival of PC3 human prostate cancer cells. Experimental Design: Adenoviruses expressing MMAC/ PTEN or green fluorescent protein as a control were introduced into PC3 cells, and effects on signal transduction pathways and growth of tumors in an orthotopic nude mouse model were determined. Results: MMAC/PTEN expression in PC3 cells decreased the level of phospho Akt but not that of phospho Mapk or FAK. Expression of MMAC/PTEN inhibited the in vitro growth of PC3 cells primarily by blocking cell cycle progression. Ex vivo introduction of MMAC/PTEN expression did not inhibit the tumorigenicity of orthotopically implanted PC3 cells, but it did significantly reduce tumor size and completely inhibited the formation of metastases. In vivo treatment of pre-established orthotopic PC3 tumors with adenoviral MMAC/PTEN did not significantly reduce local tumor size, but it did diminish metastasis formation. Conclusions: MMAC/PTEN functionally regulates prostate cancer cell metastatic potential in an in vivo model system and may be an important biological marker and therapeutic target for human prostate cancer.