B7-H4 expression promotes tumorigenesis in ovarian cancer

Int J Gynecol Cancer. 2009 Dec;19(9):1481-6. doi: 10.1111/IGC.0b013e3181ad0fa2.


Introduction: It has been previously shown that B7-H4, one of the B7 family members that serve as negative regulators of T cell function, has altered expression levels in a variety of cancers, overexpression of B7-H4 promotes cellular transformation. However, there is still lack of adequate evidence to establish a direct connection between B7-H4 expression and malignant transformation.

Methods: Herein, we constructed pE-green fluorescent protein-N1/B7-H4 mammalian expression vector and transfected into B7-H4-negative human ovarian cancer cell line SKOV3. Cellular proliferation, apoptosis, adhesion, motility, and invasion were examined in vitro. Cells injected subcutaneously into severe combined immunodeficient mouse were analyzed for the possible functions of B7-H4 in ovarian tumorigenesis in vivo.

Results: Fluorescence microscopy studies confirmed that the B7-H4-green fluorescent protein localizes in the cytoplasm of SKOV3/B7-H4 cells, whereas green fluorescent protein is uniformly distributed throughout the cell. B7-H4 promoted cellular proliferation rate and increased cell adhesion, migration, and invasion. In addition, SKOV3 cells expressing B7-H4 gained growth advantage in the xenograft model in vivo.

Conclusions: These studies demonstrate that B7-H4 directly promotes malignant transformation of ovarian cancer cell line, and provides a potential therapeutic strategy for targeting B7-H4 to inhibit progression of human ovarian cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / genetics*
  • B7-1 Antigen / metabolism
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Adhesion
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1


  • B7-1 Antigen
  • Recombinant Fusion Proteins
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human
  • Green Fluorescent Proteins