Differential expression of glutathione-s-transferase isozymes in murine and human skin tumors

Glutathione S-transferases (GSTs) are a family of widely distributed multifunctional enzymes present in a number of organs and species. GSTs participate in the detoxification of a wide variety of xenobiotics and their metabolites. Mammalian GSTs have been grouped into three major classes alpha, mu and pi. The differential expression of specific GST isozymes has been reported as a phenotypic marker for the preneoplastic lesions and neoplastic tissues in liver and other extracutaneous organs of rat and other species including humans. However, the expression of GST isozymes in skin cancer is not known. In the present study, therefore, employing Western blot analysis, we assessed the GST isozyme expression in experimentally-induced murine skin tumors and clinically obtained human skin basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). As compared to normal murine skin showing high levels of GST-pi, significantly lower expression of GST-pi was observed in murine skin papillomas and carcinomas induced chemically in SENCAR mice or by chronic ultraviolet B radiation in SKH-1 hairless mice. Similar results were also observed for GST-mu isozyme. On the other hand, compared to normal murine skin where the expression of GST-alpha isozyme was not detectable, significant levels of this GST isozyme were observed in all the murine skin papillomas and carcinomas. In case of human skin BCCs and SCCs, variable GST isozyme patterns were evident, however in each case, GST-pi was found to be significantly underexpressed as compared to that in skin from healthy subjects. Our results suggest that altered phenotypic expression of GST isozymes may be a useful marker for skin cancer.