BARX2 induces cadherin 6 expression and is a functional suppressor of ovarian cancer progression

Cancer Res. 2001 Oct 1;61(19):6977-81.

Abstract

The human homeobox BARX2 is located at 11q24-q25, within a minimal region associated with frequent loss of heterozygosity and adverse survival in epithelial ovarian cancer. BARX2 is a transcription factor that regulates transcription of specific cell adhesion molecules in the mouse. We show that BARX2 and cadherin 6 are expressed in normal human ovarian surface epithelium. BARX2 and cadherin 6 both have significantly lower expression in a clinical sample of endometrioid and clear cell ovarian cancers, as compared with serous or mixed mesodermal tumors. In a series of ovarian cancer cell lines, BARX2 expression showed a significant direct correlation with cadherin 6 expression. In OAW42, an ovarian cancer cell line that does not endogenously express BARX2, in vitro transfection of human BARX2 cDNA induced cadherin 6 expression. Transfection of BARX2 into OAW42 inhibited Matrigel invasion, haptotactic cellular migration to a collagen IV signal, and adhesion to collagen IV-coated plates. Our data demonstrate that BARX2 is expressed in the ovarian surface epithelium and has functional suppressor properties in ovarian cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics
  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Endometrioid / pathology
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Collagen / metabolism
  • Epithelium / metabolism
  • Epithelium / physiology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology
  • Humans
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • S Phase / physiology
  • Transfection
  • Tumor Cells, Cultured

Substances

  • BARX2 protein, human
  • Cadherins
  • Homeodomain Proteins
  • Collagen
  • K cadherin