Tumor Suppressor Protein TEP1/PTEN/MMAC1 and Human Breast Cancer.

摘要

We have previously cloned a novel protein, TEP1, also called PTEN or MMAC1, based on its sequence homology to members of protein tyrosine phosphatases. PTEN/MMAC1/TEP1 has now been well established as an important tumor suppressor that is commonly mutated in a wide variety of human cancers. At molecular level, PTEN/MMAC1/TEP1 protein has been shown to function as a phosphatase for phosphatidylinositol 3,4,5-trisphosphate, thus acting as a negative regulator for PI 3-kinase signaling pathway. PTEN deletions and mutations are frequently found in advanced and highly metastatic cancers, suggesting that PTEN may also play a role in preventing tumor progression and metastasis, in addition to its role as a suppressor for tumor initiation. The initiation of metastasis is usually a result of cytoskeletal rearrangements which promote enhanced cell motility. We have previously shown that genetic deletion of the Pten gene can leads to increased levels of phosphatidylinositol- 3,4,5-trisphosphate and enhanced phosphorylation of Akt. We have recently discovered that these cells also contain higher levels of the activated forms of Racl and Cdc42. Rac 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 therefore invasion associated with loss of PTEN in human breast cancer cells.