The Tumor Suppressor Protein TEP1/PTEN/MMAC1 and Human Breast Cancer
Final rept. 1 Jun 1998-31 May 2002
YALE UNIV NEW HAVEN CT
Pagination or Media Count:
PTEN is an important tumor suppressor. Both inherited mutations and somatic mutations in the PTEN gene have been frequently found in a variety of human cancers, including the breast cancer, PTEN protein has been shown to possess phosphatase activity toward phosphatidylinositol 3,4,5-trisphosphate PIP3. We have demonstrated that PTEN tumor suppressor dephosphorylates PIP3 in vivo and negatively regulates the PI 3- kinaseAkt signaling pathway. We have further shown that PTEN modulates cell cycle progression and a critical target for PTEN-regulated pathway is the CDK inhibitor p27KIP1. p27KIP1 is itself known as an Important prognosis marker for human breast cancer, We hypothesize that loss of PTEN in human cancer cells lead to reduction of p27KIP1 levels, which in turn promote cell cycle progression and tumorigenesis. We have also demonstrated that PTEN controls cell motility, and such regulation is mediated through regulation of the activities of Racl and Cdc42. Racl and Cdc42 are two small GTPases that have been implicated in cell motility and tumor invasion processes. Our studies have provided a molecular explanation for the increased cell motility and thus invasion associated with loss of PTEN in human breast cancer cells.
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