Role of activating transcription factor (ATF-2) in breast cancer: a possible cross talk with CYP2C19*17 allele

Abstract

CYP2C19 plays a key role in the metabolism of estrogen. Promoter polymorphism of CYP2C19 (*17, -806C>T) causing ultra rapid metabolizer phenotype for estrogen, may reduce the risk of breast cancer. Activating transcription factor (ATF-2) is plays an important a role in tumorigenesis. Estrogens influence the transcription of ATF-2 which again plays a role in the expression of several tumor suppressor and tumorigenic proteins. ATF-2 acts generally on tumour suppressor genes in mammary tissue but can also undergo estrogen mediated increased phosphorylation acting on tumorigenic genes, thus showing dual actions. We hypothesize that presence of CYP2C19*17 allele may enhance ATF-2 binding to its promoter region, hence may increase the expression of CYP2C19 causing more rapid metabolism of estrogens, protecting from the occurrence of breast cancer. Increased activity of CYP2C19 in the presence of CYP2C19*17 allele may alter the levels of phosphorylated ATF-2 by reducing the estrogen levels, leading to the increased transcription of tumorsupressor genes. This will lead to decreased incidence of breast cancer in individuals carrying CYP2C19*17 allele.