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BARX2 Induces Cadherin 6 Expression and Is a Functional Suppressor of Ovarian Cancer Progression¹

Imperial Cancer Research Fund Medical Oncology Unit and University of Edinburgh Department of Clinical Oncology [G. C. S., L. L., K. P. W., G. J. R., E. A. S., E. P. M., J. F. S., H. G.] and Medical Genetics Section, Department of Medical Sciences [D. J. P.], University of Edinburgh Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, United Kingdom, and Oncology Centre, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 [B. D. N.]

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.

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