Because NRG1mediated adhesion and migration is PI3KAKT1dependent , the findings from our previous studies led us to hypothesize that there may possibly be a practical connection concerning COMT and AKT1. Interestingly, the two COMT and AKT1 have also been implicated within the pathogenesis of cancer and schizophrenia, and their associations with these disorder conditions have been extensively studied . COMT catalyzes the transfer within the methyl group of Sadenosylmethionine to a hydroxyl group on a assortment of catechols, together with the catecholamine neurotransmitters and carcinogenic catechol estrogen compounds . A G to A transition at COMT codon 108/158 translates a valine to methionine substitution that codes for high and very low activity proteins, respectively . A variety of research have shown that the large activity Val allele is associated with comparatively poorer function of prefrontal cortex, in contrast together with the Met kind .
Despite the fact that results have already been inconsistent, the Val allele has also been sometimes implicated like a danger element for schizophrenia . Similarly, some research have also proven an association of Val108/ 158Met with breast cancer and prostate cancer ; the very low exercise Met allele is usually selleck reversible STAT inhibitor related with improved threat of metastasis and poorer prognosis. Recent proof signifies that you will find other practical variants in COMT that modulate the biologic results of the Val/Met polymorphism and confound simple Val/Met associations . AKT1 is usually a serine/threonine kinase that functions as a central element inside the cell survival pathway and is activated in many cancers . Not too long ago, a Glu to Lys mutation at amino acid 17 within the AKT1coding sequence continues to be recognized in breast, colon and ovarian cancers, suggesting that this mutation may possibly bring about 28% of cancers of these forms .
The AKT1 gene has also been linked with schizophrenia. Emamian and colleagues demonstrated diminished AKT1 protein expression in B lymphoblasts and postmortem brain tissues from patients with schizophrenia. In addition they supplied the first evidence of association in between AKT1 and schizophrenia in Caucasians based on 5 SNPs spanning LY2940680 Hedgehog inhibitor this gene. No less than six subsequent studies and onemeta analysis have supplied supportive proof for this association. Even more, a coding and riskassociated polymorphism continues to be related with low expression from the protein and improved susceptibility to apoptosis in B lymphoblasts .
AKT1 also is implicated in dopamine signaling in brain , as well as a recent imaging review of ordinary topics suggested that COMT and AKT1 interact with the degree of cortical physiology related to dopamine function . In spite of the overlap of COMT and AKT1 in associations with cancer and schizophrenia, molecular and cell biological interactions of COMT and AKT1 haven’t been explored.