A novel tumor suppressor gene, PTEN, has recently been identified at chromosome 10q23, which is inactivated in a number of different tumor types including breast cancer. An investigation of the functional role suggested that PTEN transcriptionally represses both exogenous and endogenous c-myc expressions in human breast carcinoma cells. PTEN, when ectopically expressed in human breast carcinoma cells, exhibited an inhibition of phosphorylation of both activating residues of protein kinase B (PKB)/AKT at Ser-473 and Thr-308 without any significant alteration of AKT expression. Furthermore, introduction of PTEN into human breast carcinoma cells induced apoptotic cell death and inhibited cell growth and tumor formation in nude mice. Taken together, our data suggest that PTEN acts as a transcriptional repressor, inhibits the AKT-mediated cell survival signaling pathway, and negatively regulates human breast carcinoma cell growth. These results further emphasize the potential of PTEN as a gene therapeutic agent. (C) 1999 Elsevier Science B.V. All rights reserved.
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