Disease relevance of BARX2

• To begin to identify the gene targets that mediate its effects, chromatin immunoprecipitation (ChIP) was used to isolate BARX2 binding sites from the human MCF7 breast cancer cell line [1].
• Our data demonstrate that BARX2 is expressed in the ovarian surface epithelium and has functional suppressor properties in ovarian cancer cells [2].
• 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 [3].

High impact information on BARX2

• To identify proteins that bind to a regulatory element common to the genes for two neural CAMs, Ng-CAM and L1, we screened a mouse cDNA expression library with a concatamer of the sequence CCATTAGPyGA and found a new homeobox gene, which we have called Barx2 [4].
• The localization data, combined with Barx2's dual function as activator and repressor, suggest that Barx2 may differentially control the expression of L1 and other target genes during embryonic development [4].
• In OAW42, an ovarian cancer cell line that does not endogenously express BARX2, in vitro transfection of human BARX2 cDNA induced cadherin 6 expression [2].
• BARX2 is a transcription factor that regulates transcription of specific cell adhesion molecules in the mouse [2].
• Transfection of BARX2 into OAW42 inhibited Matrigel invasion, haptotactic cellular migration to a collagen IV signal, and adhesion to collagen IV-coated plates [2].

Chemical compound and disease context of BARX2

• The aim of this study was to define whether BARX2 could modulate sensitivity to cisplatin in human epithelial ovarian cancer [3].

Biological context of BARX2

• BARX2 is localized on human chromosome 11q25, as determined by radiation hybrid mapping [5].
• The human BARX2 gene: genomic structure, chromosomal localization, and single nucleotide polymorphisms [5].
• Cloning and sequencing of BARX2-ChIP-derived DNA fragments identified 60 potential BARX2 target loci that were proximal to or within introns of genes involved in cytoskeletal organization, cell adhesion, growth factor signaling, transcriptional regulation, and RNA metabolism [1].
• A combination of sequence analysis and electrophoretic mobility shift assays revealed homeodomain binding sites within several fragments that bind to BARX2 in vitro [1].
• Mutation analyses of three fragments showed that their transcriptional activities required the HBS, and suggested that BARX2 regulates gene expression by binding to DNA elements containing paired TAAT motifs that are separated by a poly(T) sequence [1].

Anatomical context of BARX2

• BARX2 is highly expressed in adult salivary gland and is expressed at lower levels in other tissues, including mammary gland, kidney, and placenta [6].
• We speculate that Barx2 may regulate cell adhesion molecules in epithelial cells of the gut [7].
• Barx2 was expressed in muscle cells of the muscularis externa and also showed a graded pattern of expression in intestinal enterocytes, decreasing in a crypt-to-villous direction [7].
• By Northern blotting and in situ hybridization, we show that Barx2 is expressed throughout the gut and is located in epithelial cells of the proliferative and differentiative regions of the stomach, esophagus, and intestine [7].

Associations of BARX2 with chemical compounds

• 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 [3].

Other interactions of BARX2

• Based on the coexpression, BARX2 was assumed to be a candidate gene for those cases of Rieger syndrome that cannot be associated with mutations of PITX2 [5].
• BARX2 is a homeobox transcription factor that influences cellular differentiation in various developmental contexts [1].
• In addition, BARX2 expression promotes cellular invasion and increases the expression of active matrix metalloproteinase-9 (MMP9) [8].
• Overall, these data indicate that BARX2 and ESR1 may coordinately regulate cell growth, survival and invasion pathways that are critical to breast cancer progression [8].

References