title: PTEN/PI3K/mTOR/B7-H1 signaling pathway regulates cell progression and immuno-resistance in pancreatic cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.forename: Yingfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianlong
authors.initials: J
authors.lastname: Zhang
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Xiao
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Junyao
authors.initials: J
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Qibing
authors.initials: Q
authors.lastname: Tang
mesh_terms: D017209:Apoptosis; D060890:B7-H1 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D019139:Tumor Escape
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human