BARX2 induces cadherin 6 expression and is a functional suppressor of ovarian cancer progression.
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.
Sellar
G C
GC
Imperial Cancer Research Fund Medical Oncology Unit and University of Edinburgh Department of Clinical Oncology, Edinburgh EH4 2XU, United Kingdom.
Li
L
L
Watt
K P
KP
Nelkin
B D
BD
Rabiasz
G J
GJ
Stronach
E A
EA
Miller
E P
EP
Porteous
D J
DJ
Smyth
J F
JF
Gabra
H
H
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
C491320:BARX2 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D003094:Collagen; C087310:K cadherin