BCAR1 ELISA Kit

The expression of Prostate Specific-Membrane Antigen (PSMA) increases in high-grade prostate carcinoma envisaging a role in growth and progression. We show here that clustering PSMA at LNCaP or PC3-PSMA cell membrane activates AKT and MAPK pathways thus promoting proliferation and survival. PSMA activity was dependent on the assembly of a macromolecular complex including filamin A, beta1 integrin, p130CAS, c-Src and EGFR. Within this complex beta1 integrin became activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y-1086 and Y-1173 EGF-independent residues. Silencing or blocking experiments with drugs demonstrated that all the complex components were required for full PSMA-dependent promotion of cell growth and/or survival in 3D culture, but that p130CAS and EGFR exerted a major role. All PSMA complex components were found assembled in multiple samples of two high-grade prostate carcinomas and associated with EGFR phosphorylation at Y-1086. The expression of p130CAS and pEGFR(Y1086) was thus analysed by tissue micro array in 16 castration-resistant prostate carcinomas selected from 309 carcinomas and stratified from GS 3+4 to GS 5+5. Patients with Gleason Score <= 5 resulted negative whereas those with GS >= 5 expressed p130CAS and pEGFR(Y1086) in 75% and 60% of the cases, respectively. Collectively, our results demonstrate for the first time that PSMA recruits a functionally active complex which is present in high-grade patients. In addition, two components of this complex, p130CAS and the novel pEGFR(Y1086), correlate with progression in castration-resistant patients and could be therefore useful in therapeutic or surveillance strategies of these patients.

Context: Recently, 10 novel type 2 diabetes (T2D) susceptibility single nucleotide polymorphisms (SNPs) in ZMIZ1, ANK1, KLHDC5, TLE1, ANKRD55, CILP2, MC4R, BCAR1, HMG20A, and GRB14 loci were discovered in MetaboChip-genotyped populations of European ancestry. Objective: The aim of the present study was to characterize prediabetic quantitative traits underlying these SNP associations and to calculate the amount of interindividual variation in glycemic traits explained by these and previous T2D susceptibility variants. Design and Participants: A total of 5739 Danish individuals naive to glucose-lowering medication were included in quantitative trait studies, and case-control analyses were performed in 1892 patients with T2D and 6603 normoglycemic control subjects. Participants without known T2D underwent an oral glucose tolerance test, and measures of insulin release and sensitivity were estimated from insulinogenic, disposition, BIGTT, and Matsuda indexes. Results: We confirmed associations of ZMIZ1, KLHDC5, CILP2, HMG20A, ANK1, ANKRD55, and BCAR1 with T2D. The risk T allele of BCAR1 rs7202877 associated with decreased disposition index (P = .02). The C allele of ANK1 rs516946 associated with decreased insulinogenic (P = .005) and disposition (P = .002) indexes. The G allele of ANKRD55 rs459193 associated with decreased Matsuda index (P = .02) adjusted for waist circumference. The C allele of GRB14 rs13389219 associated with both increased insulinogenic (P = .04) and decreased Matsuda (P = .05) indexes. All validated European T2D variants still only explained a few percentage points of glycemic trait variation. Conclusions: BCAR1 rs7202877 may mediate its diabetogenic impact through impaired beta-cell function, but this finding needs to be replicated in independent studies. In addition, we substantiated previous evidence that ANK1 rs516946 confers impaired insulin release and that ANKRD55 rs459193 and GRB14 rs13389219 associate with insulin resistance. (J Clin Endocrinol Metab 98: E801-E806, 2013)