Overexpression of B7-H1 correlates with malignant cell proliferation in pancreatic cancer

Oncol Rep. 2014 Mar;31(3):1191-8. doi: 10.3892/or.2013.2955. Epub 2013 Dec 31.

Abstract

B7-H1, a member of the B7 family of proteins, is hypothesised to play an important role in the immune escape of tumours through its binding to the PD-1 receptor on activated T and B cells. By inducing T lymphocyte apoptosis, tumour cells can suppress an effective antitumour immune response. Although the immunosuppressive effect of B7-H1 has been studied in many tumours, its other biological functions remain unclear. We previously demonstrated a high expression level of this molecule in pancreatic cancer patient samples and its antiapoptotic effect in pancreatic ductal adenocarcinoma (PDA) cells. The aim of the present study was to investigate the possible role of B7-H1 in the proliferation of PDA cells. Functional studies were performed using pancreatic cell lines that were genetically engineered to express high or low levels of B7-H1, and we found that the overexpression of B7-H1 through plasmid transfection in PDA cells promoted cell proliferation. Conversely, the short-hairpin RNA (shRNA) knockdown of B7-H1 inhibited PDA cell proliferation. Further analyses of the cell cycle and cell cycle-related molecules confirmed this result. Taken together, our results indicate that the upregulation of B7-H1 in pancreatic cancer cells promotes proliferation and accelerates carcinogenesis; these data, therefore, provide insights into the effects of B7-H1 overexpression on pancreatic tumour cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Carcinogenesis / metabolism
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin D1 / metabolism
  • Epithelial-Mesenchymal Transition
  • G2 Phase Cell Cycle Checkpoints
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Kinase 4 / metabolism
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Up-Regulation

Substances

  • B7-H1 Antigen
  • CCND1 protein, human
  • CD274 protein, human
  • Cyclin D1
  • MAP Kinase Kinase 4