title: The homeobox gene BARX2 can modulate cisplatin sensitivity in human epithelial ovarian cancer.
abstract: Epithelial ovarian cancer (EOC) is the most common cause of death from gynaecological malignancy. Resistance to platinum chemotherapy is a major reason for treatment failure and poor prognosis. The human homeobox gene BARX2 is located within a minimal region at 11q25 that is associated with frequent loss of heterozygosity (LOH) and adverse survival in EOC. BARX2 is a transcription factor known to regulate transcription of specific cell adhesion molecules in the mouse. We have previously shown that BARX2 expression is low in clear cell/endometrioid and high in serous adenocarcinomas of the ovary, histologic variants that are less and more sensitive, respectively to platinum chemotherapy. The aim of this study was to define whether BARX2 could modulate sensitivity to cisplatin in human epithelial ovarian cancer. In two cell line series sequentially derived from ovarian cancer patients pre- and post-cisplatin chemotherapy, BARX2 expression was downregulated in the cell lines established upon tumor recurrence after platinum therapy. Transfection of BARX2 into a platinum resistant cell line significantly reversed cisplatin resistance compared with its isogenic platinum sensitive parent, in both growth inhibition and clonogenic assays. Taken together, our data demonstrate that the homeobox gene BARX2 may be a biological factor involved in determining sensitivity or resistance to the cytotoxic effects of cisplatin.
authors.affiliation: Cancer Research UK Edinburgh Oncology Unit and University of Edinburgh Department of Clinical Oncology, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, Scotland, UK.
authors.forename: Grant C
authors.initials: GC
authors.lastname: Sellar
authors.forename: Karen P
authors.initials: KP
authors.lastname: Watt
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Barry D
authors.initials: BD
authors.lastname: Nelkin
authors.forename: Genevieve J
authors.initials: GJ
authors.lastname: Rabiasz
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: John F
authors.initials: JF
authors.lastname: Smyth
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
mesh_terms: D015152:Blotting, Northern; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C491320:BARX2 protein, human; D018398:Homeodomain Proteins; D002945:Cisplatin