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  • Title: PTEN/PI3K/mTOR/B7-H1 signaling pathway regulates cell progression and immuno-resistance in pancreatic cancer.
    Author: Zhang Y, Zhang J, Xu K, Xiao Z, Sun J, Xu J, Wang J, Tang Q.
    Journal: Hepatogastroenterology; 2013 Oct; 60(127):1766-72. PubMed ID: 24624456.
    Abstract:
    BACKGROUND/AIMS: Patients of Pancreatic Cancer with B7-H1 over-expression usually have a poor prognosis. In our previous study, the expression of PTEN and B7-H1 were significantly correlated to the carcinogenesis in pancreatic carcinoma. In this study, we investigated the role of the PTEN/mTOR/B7-H1 pathway in immune-resistance, immune escape and progression of pancreatic cancer. METHODOLOGY: siRNAs targeting PTEN were designed, and transfected into pancreatic cancer cell lines. Transwell chamber invasion assay, CCK-8 proliferation assay and siRNA interference assay were used to explore the effect of PTEN on PI3K signaling. Expression of protein and mRNA of the factors involved in PTEN/mTOR/B7-H1 pathway were examined by RT-PCR and Western blot. T Cells apoptosis assay were performed by flow cytometer. RESULTS: Our study demonstrated that B7-H1 was regulated by PTEN through the PI3K/AKT pathway. Loss of PTEN promoted cell proliferation, cell invasion and led to significant increases in the levels of Phospho-AKT, Phospho-mTOR, phospho-S6K1 and B7-H1 proteins. In addition, the increased expression level of B7-H1 when PTEN was knockdown induced T lymphocyte apoptosis. CONCLUSION: Our results demonstrated deletion of PTEN in pancreatic cancer cells induced the expression of B7-H1, which contributed to immune suppression and increased cancer progression and invasion.
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