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.
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.
Authors: Selvi Kunnimalaiyaan; Jose Trevino; Susan Tsai; T Clark Gamblin; Muthusamy Kunnimalaiyaan Journal: Mol Cancer Ther Date: 2015-04-17 Impact factor: 6.261
Authors: Anna Sophie Berghoff; Barbara Kiesel; Georg Widhalm; Orsolya Rajky; Gerda Ricken; Adelheid Wöhrer; Karin Dieckmann; Martin Filipits; Anita Brandstetter; Michael Weller; Sebastian Kurscheid; Monika E Hegi; Christoph C Zielinski; Christine Marosi; Johannes A Hainfellner; Matthias Preusser; Wolfgang Wick Journal: Neuro Oncol Date: 2014-10-29 Impact factor: 12.300
Authors: Marissa Williams; Michaela B Kirschner; Yuen Yee Cheng; Jacky Hanh; Jocelyn Weiss; Nancy Mugridge; Casey M Wright; Anthony Linton; Steven C Kao; J James B Edelman; Michael P Vallely; Brian C McCaughan; Wendy Cooper; Sonja Klebe; Ruby C Y Lin; Himanshu Brahmbhatt; Jennifer MacDiarmid; Nico van Zandwijk; Glen Reid Journal: Oncotarget Date: 2015-09-15