| IntroductionPTEN is a tumor suppressor gene that maps to the 10q23. 3 interval. The protein product, PTEN, shares homology with the cytoskele-tal protein tensin and the secretory vesicle protein auxilin and also with dual specificity phosphatases. Indeed, recombinant PTEN exhibits activity against both phosphophotyrosine - and phosphothreonine -containing protein substrates. Overexpression of PTEN suppresses tumor colony formation in certain cell lines and can suppress tumor formation in nude mice. PTEN overexpression can also negatively regulate cellular adhesion and cell mobility on fibronectin - coated plates. This activity may result from PTEN -mediated dephosphoryla-tion of focal adhesion kinase. PTEN may also alter mitogen - activated protein kinase signaling.PTEN can also act as a lipid phosphatase. Specifically, PTEN can dephosphorylate phosphotidylinositol 3,4,5 - trisphosphate and phosphotidylinositol 3,4- trisphosphate, which are both direct products of PDK activity. Researches have shown that PTEN can inhibit cell cycle progression and induce a Gl arrest. This function appears to require the lipid phosphatase activity of PTEN, resulting in the negative regulation of the PI3K/Akt signaling pathway. A significant in-crease in the level of the cell cycle kinase inhibitor p27KIP1 occurs with concomitant decreases in G1 cyclin - dependent kinase activity upon the introduction of PTEN into human glioblastoma U87MG cells, suggesting that p27 may be a target of the PTEN cell cycle arrest pathway. In keeping with these data, heterozygous loss of the murine PTEN gene ( mPTEN) leads to an increase in the mitotic index and the Ki - 67 staining index in the murine prostate . In addition, PTEN negatively regulates Akt - dependent cell survival . Akt is one of the key regulatory molecules involved in the protection of cells against ap-optosis. These data support the idea that PTEN negatively regulates cell growth and/or proliferation through its ability to act as an in vivo phosphoinositide 3 - phosphatase, thus negatively regulating the PIS K/Akt signaling pathway.Osteosarcoma is the most prevalent malignancy bone tumor in human and often threatens adult and adolescence . Pathological stage are important predictors of prognosis in patients with osteosarcoma who undergo radical operation. Osteosarcoma, however, is a remarkably heterogeneous disease. Distinguishing tumors associated with a poor outcome at the time of radical operation is problematic. The molecular mechanisms of bone carcinogenesis remain poorly understood. LOH of 10q has been reported to occur in tumor with a high frequency, and two distinct, commonly deleted regions have been identified at 10q22 q24 and 10q25, respectively, implying the presence of putative tumor suppressor genes at these loci .Homozygous deletions and somatic mutations of PTEN have been iden - tified in many tumor cell lines and tumor specimens. Marked heterogeneity of PTEN alterations has been observed in metastatic tumor tissues. Loss of PTEN expression is more frequently detected inxenografts of cell lines . PTEN may be inactivated by mechanisms other than gene deletion and mutations, including promoter methylation or translational modification . However, other groups failed to detect PTEN methylation in prostate, bladder, and renal cell cancer with LOH of 10q when a PCR - based assay was used.In this study, we wanted to assess the extent of loss of the PTEN protein in osteosarcoma using immunohistochemistry. We analyzed the pattern of immunohistochemical staining in 43 cases of paraffin - embedded resected osteosarcoma using a murine monoclonal antibody to PTEN. Detection of PTEN protein was correlated with the pathological stage of the tumor.Materials and MethodsMaterialWe used cases from a bone tumor database consisting of 25 paraffin - embedded osteosarcoma and 30 paraffin - embedded osteoen-chondroma that had been collected in the Department of Pathology, the first clinical hospital China Medical University, dating from 1995 1999. 18 cases wer...
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