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Hepatogastroenterology. 2013 Oct;60(127):1766-72.

PTEN/PI3K/mTOR/B7-H1 signaling pathway regulates cell progression and immuno-resistance in pancreatic cancer.

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.

PMID:
24624456
[Indexed for MEDLINE]

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