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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • B7-H1 Antigen / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Coculture Techniques
  • Humans
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphorylation
  • RNA Interference
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • TOR Serine-Threonine Kinases / metabolism*
  • Time Factors
  • Transfection
  • Tumor Escape*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • MTOR protein, human
  • Phosphatidylinositol 3-Kinase
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 1
  • PTEN Phosphohydrolase
  • PTEN protein, human