Magic™ Anti-BCAR1 (Phospho Y751) polyclonal antibody

Two recent studies found that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 are related to type 2 diabetes. However, the association of these loci with type 2 diabetes mellitus (T2DM) has not been examined in Chinese. We performed a replication study to investigate the association of the 2 susceptibility loci with T2DM in the Chinese population. We genotyped 1961 Chinese participants (991 with T2DM and 970 controls) for each of the 2 single nucleotide polymorphisms (SNPs) rs7593730 in RBMS1 and rs7202877 near BCAR1 using SNPscan and examined their association with T2DM using logistic regression analysis. We also analyzed the correlation of the SNP alleles and clinical phenotypes. In additive model, genotype association analysis of BCAR1 rs7202877 loci revealed that the homozygous of rs7202877 GG carriers had significantly decreased T2DM risk compared to homozygous carriers of TT (P=0.038, OR 0.44, 95% CI 0.20-0.96). In the recessive model, the GG genotype GG had significantly decreased T2DM risk compared to GT+TT (P=0.043, OR 0.67, 95% CI 0.46-0.99). Allele G was statistically significantly correlated with TC (mmol/L) (P=0.036) and LDL-C (mmol/L) (P=0.007). As for rs7593730, the carriers of CT and TT genotype had significantly decreased T2DM risk compared to the carriers of CC genotype (CT: CC P=0.038, OR 0.71, 95% CI 0.51-0.98; TT: CC P=0.010, OR 0.32, 95% CI 0.13-0.76). In a dominant model, TT+CT: CC (P=0.013, OR 0.673, 95% CI 0.49-0.92) and in a recessive model, TT: CT+CC (P=0.019, OR 0.59, 95% CI 0.39-0.92). The T allele carriers had significantly decreased T2DM risk compared to the carriers of C (P=0.002, OR 0.65, 95% CI 0.50-0.86). Allele T was statistically correlated with FINS (P=0.010). In conclusion, our study showed that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 were significantly associated with type 2 diabetes in the Chinese population.

Background: Treatment of breast cancer with the antiestrogen tamoxifen is effective in approximately one half of the patients with estrogen receptor-positive disease, but tumors recur frequently because of the development of metastases that are resistant to tamoxifen. We have previously shown that mutagenesis of human estrogen-dependent ZR-75-1 breast cancer cells by insertion of a defective retrovirus genome caused the cells to become antiestrogen resistant, In this study, we isolated and characterized the crucial gent at the breast cancer antiestrogen resistance 1 (BCAR1) locus. Methods/Results: Transfer of the BCAR1 locus from retrovirus-mutated, antiestrogen-resistant cells to estrogen-dependent ZR-75-1 cells by cell fusion conferred an antiestrogen-resistant phenotype on the recipient cells, The complete coding sequence of BCAR1 was isolated by use of exon-trapping and complementary DNA (cDNA) library screening, Sequence analysis of human BCAR1 cDNA predicted a protein of 870 amino acids that was strongly homologous to rat p130Cas-adapter protein. Genomic analysis revealed that BCAR1 consists of seven exons and is located at chromosome 16q23.1. BCAR1 transcripts were detected in multiple human tissues and were similar in size to transcripts produced by retrovirus-mutated ZR-75-1 cells. Transfection of BCAR1 cDNA into ZR-75-1 cells again resulted in sustained cell proliferation in the presence of antiestrogens, confirming that BCAR1 was the responsible gene in the locus. Conclusions: Overexpression of the BCAR1 gene confers antiestrogen resistance on human ZR-75-1 breast cancer cells. Overexpression of BCAR1 in retrovirus-mutated cells appears to result from activation of the gene's promoter, The isolation and characterization of this gene open new avenues to elucidating mechanisms by which the growth of human breast cancer becomes independent of estrogen.