| Phosphorylation and dephosphorylation almost involved in all physiological and pathological process in cell and play an important role in signal transfer process. The disharmony of phosphorylation and dephosphorylation will lead up to cell carcinomatous change. Phosphatase and tensin homology deleted on chromosome ten (PTEN) gene was the first tumor suppressor gene that encodes a 403 amino acid dual specificity phosphatase containing a region of homology to tensin and auxillin and has gained widely attention from discovered. PTEN gene can make phosphatidylinositol -3,4,5-triphosphate [Ptd Ins(3,4,5)P3] dephosphorylation specifically and participate in cell growth, proliferation and the interaction of extracellular matrix. Many oncogene's product is protein kinase that phosphatase can inhibit the effect of it. But we cannot approve the function of phosphatase in tumor occurrence directly until we study the PTEN gene. The study corroborated that lack of active phosphatase will add the dangerous of tumor occurrence for the first time. So PTEN gene is another important tumor suppressor gene that we should pay our attention to after pRb,p53 gene. PTEN gene has these functions after research: Participate in the development of embryo；Inhibit cell growth through block Pre-DNA-synthetic gap or induce cell apoptosis；Inhibit the activity of telomerase；Inhibit cell migration, spread out and adhesiveness. 1,PTEN gene and signal transduction Latest study shows that as a phosphatase, PTEN gene can make the inositol ring D3 of Ptd Ins(3,4,5)P3 and Ptd Ins(3,4)P2 dephosphorylation to form Ptd Ins(4,5)P2 and Ptd Ins(4)P. These D3 phospholipid is the direct products of phosphatidylinositol 3-OH kinase (PI3K). PI3K/Ptd Ins(3,4,5)P3 accomplishes the signal transduction that related to cell growth and survival through many approaches. 2,PTEN gene induces the block of cell cycle There are two mechanisms that PTEN gene may induces cell growth suppression: 1)To promote cell cycle block in Pre-DNA-synthetic gap；It has been confirmed that the block depends on AKT and can restore by active AKT. 2) Accelerate cell apoptosis induces by many stimulate.3,PTEN gene as a apoptosis factorPTEN gene can restrain tumor occurrence by increase cell apoptosis rate except inducing the block of cell cycle. We had introduced over expressed PTEN gene into the mice cell that PTEN gene was deleted and found that its sensibitity to ultraviolet radiation, hot shock and the apoptosis induced by radiation was increased.4,PTEN gene and cell migration PTEN gene can inhibit cell transfer, diffusion and adhering together. This effect is related to the block of integrin signal pathway. Integrin can bind and gather focal-adhension kinase (FAK) through formatting cellular skeleton compound and then activates FAK by phosphorylating the tyrosine. Activated FAK regulates Ras-mitogen activated protein kinase (MAPK) pathway coupling by adapter protein thus mediates cell adhesiveness and transfer. PTEN gene binds to the same compound as FAK and dephosphorylates the tyrosine. PTEN gene also can block MAPK pathway by suppress Shc phosphorylation. Latest study indicated that both FAK and Shc could mediate PTEN gene to inhibit cell migration. FAK related to directional migration and Shc related to random migration. Another study shows that the protein ERBB-2 of oncogene erb may related to the effect of PTEN gene inhibits cell migration.A great deal of investigation has indicated that PTEN gene has mutation or deletion in many tumors. When cloning PTEN gene, some scholars detected the mutation of it in many tumors at the same time. They found that the mutation rate of PTEN gene was 31% in glioblastoma cell strain and secondary tumor, 17% in primary tumor, 100% in prostatic adenocarcinoma cell strain and 6% in breast cancer cell strain. Liu and Rasheed's investigation showed that there was homologous deletion of PTEN gene in 30% primary glioblastoma, 50%～60% in glioblastoma cell strain and no deletion in low differentiative glioblastoma. This co... |
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