Relevance and Therapeutic Possibility of PTEN-Long in Renal Cell Carcinoma
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PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance.Keywords:
Tensin
Phosphatase and tensin homolog gene(PTEN)was identified as a tumor suppressor located in 10q23 with dual phosphatase activity,its deleted or inactivation often leads to cancer.PTEN express widely in nervous system,which lipid and protein phosphatase activities can regulate neuronal injury and incidence of brain dysfunction through Akt signaling pathway and interaction with the membrane receptor N-methyl-D-aspartate receptor and 5-hydroxytryptamine2c receptor.So,the further study of PTEN will have potential clinical value in the treatment of cancer and neurological diseases.
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Phosphatase and tensin homolog deleted on chromosome ten(PTEN),one of the mostly investigated tumor suppressor genes,has a close correlation with tumorigenesis.The activation of PI3K-AKT pathway caused by abnormal PTEN is one of the major mechanisms underlying tumor occurrence.Therefore,PTEN regulation is important for uncovering new mechanisms of tumor occurrence and establishing novel therapeutic strategies.The cellular PTEN regulations including transcriptional regulation,post-transcriptional modulation,post-translation modification and protein-protein interaction are reviewed in this paper.
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PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumour suppressor that functions as a PtdIns(3,4,5)P3 3-phosphatase to inhibit cell proliferation, survival and growth by antagonizing PI3K (phosphoinositide 3-kinase)-dependent signalling. Recent work has begun to focus attention on potential biological functions of the protein phosphatase activity of PTEN and on the possibility that some of its functions are phosphatase-independent. We discuss here the structural and regulatory mechanisms that account for the remarkable specificity of PTEN with respect to its PtdIns substrates and how it avoids the soluble headgroups of PtdIns that occur commonly in cells. Secondly we discuss the concept of PTEN as a constitutively active enzyme that is subject to negative regulation both physiologically and pathologically. Thirdly, we review the evidence that PTEN functions as a dual specificity phosphatase with discrete lipid and protein substrates. Lastly we present a current model of how PTEN may participate in the control of cell migration.
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PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumour suppressor that functions as a PtdIns(3,4,5)P3 3-phosphatase to inhibit cell proliferation, survival and growth by antagonizing PI3K (phosphoinositide 3-kinase)-dependent signalling. Recent work has begun to focus attention on potential biological functions of the protein phosphatase activity of PTEN and on the possibility that some of its functions are phosphatase-independent. We discuss here the structural and regulatory mechanisms that account for the remarkable specificity of PTEN with respect to its PtdIns substrates and how it avoids the soluble headgroups of PtdIns that occur commonly in cells. Secondly we discuss the concept of PTEN as a constitutively active enzyme that is subject to negative regulation both physiologically and pathologically. Thirdly, we review the evidence that PTEN functions as a dual specificity phosphatase with discrete lipid and protein substrates. Lastly we present a current model of how PTEN may participate in the control of cell migration.
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PTEN(Phosphatase and Tensin Homology deleted from Chromosome ten),a putative antioncogene,encodes a PTEN protein that has a dual specificity phosphatase activity with both protein phosphatase and lipid phosphatase,which regulates a variety of molecules through inhibiting the PI3K/Akt signaling pathway.Recently,some scholars dedicate to the modulation of PTEN,which demonstrates that PTEN can be regulated by multiple factors at the level of gene and protein.This review briefly summarizes up-to-date information about the modulation of PTEN and its mechanisms.
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Objective To investigate whether the expression of phosphatase and tensin homolog deleted on chromosome ten( PTEN) is involved in the initiation and progression of non-smallcell lung carcinoma( NSCLC). Methods The expression of PTEN was detected in 45 paired NSCLC tumor and adjacent normal tissues by immunohistochemistry. Results The positive expression rates of PTEN in NSCLC tumor and normal tissues were 31. 1% and 66. 7% respectively,the difference was statistically significant( P = 0. 001). PTEN expressions correlated with the differentiation of the tumor( P = 0. 000). Conclusion Lack of PTEN expression may be involved in the initiation and progression of NSCLC.
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