Anti-PIK3R1 monoclonal antibody, clone FQS6624 Knockout Validated

Longevity is a polygenic trait in which genetic predisposition is particularly important. We hypothesized that among genes differentially expressed in response to caloric restriction, several may be candidate longevity genes. We tested 459 single-nucleotide polymorphisms (SNPs) in 47 genes differentially expressed in calorically restricted mice and 12 other genes for association with longevity. Subjects were American men of Japanese ancestry, 440 aged >= 95 years and 374 with an average life span. Based on a dominant model of inheritance, an association with longevity at the p < .05 level was seen for SNPs in 13 of the genes. Testing by all possible models increased the number of genes to 18. After correction for multiple testing, four genes retained significance, namely, MAP3KS (p = .00004), SIRT7 (p = .00004), SIRTS (p = .0007), and PIK3R1 (p ..01). In a dominant model, association with longevity was seen for multiple adjacent SNPs within two of these genes (MAP3K5 and PIK3R1), as well as in FLT1, consistent with linkage disequilibrium with a causative variant in the vicinity of each respective SNP set. MAP3K5 and FLT1 haplotypes were associated with longevity. In conclusion, the present study implicates variation in MAP3K5, FLT1, PIK3R1, SIRT7, and SIRT5 in human longevity.

The phosphoinositide-3 kinase (PI3K) pathway plays a critical role in cancer cell growth and survival and has also been implicated in the development of the childhood cancer neuroblastoma. In neuroblastoma high mRNA expression of the PI3K catalytic isoform PIK3CD is associated to favorable disease. Yet, activation of Akt is associated with poor prognosis. Since the contribution of the numerous members of this pathway to neuroblastoma pathogenesis is mainly unknown, genes of the PI3K/Akt pathway were analyzed at the mRNA level through microarrays and quantitative real-time RT-PCR (TaqMan) and at the protein level using western blot analysis. Five genes showed lower mRNA expression in aggressive compared to more favorable neuroblastomas (PRKCZ, PRKCB1, EIF4EBP1, PIK3RI and PIK3CD) while the opposite was seen for PDGFRA. Clustering analysis shows that the expression levels of these six genes can predict aggressive disease. At the protein level, p110 delta (encoded by PIK3CD) and p85 alpha isomers (encoded by PIK3R1) were more highly expressed in favorable compared to aggressive neuroblastoma. Evaluation of the expression of these PI3K genes can predict aggressive disease, and indicates stage-dependent involvement of PI3K-pathway members in neuroblastoma.