[Usefulness of glutathione S-transferase as a tumor marker]

Abstract

The glutathione S-transferases (GSTs), a family of multifunctional proteins, catalyze the glutathione conjugation reaction with electrophilic compounds biotransformed from xenobiotics, including carcinogens, and are grouped into four classes, Alpha, Mu, Pi and Theta. Some of these forms are suggested to act to prevent carcinogenesis by detoxifying proximate or ultimate carcinogens. In neoplastic cells, specific forms are known to be expressed and have been known to participate in their resistance to anticancer drugs. In this article, we review recent findings regarding the respective molecular forms involved in carcinogenesis and their usefulness as tumor markers. GST M1 and GST T1 genes are polymorphic in the population and losses of these genes have been suggested as possible markers for greater susceptibility to lung cancer among smokers and several other cancers. Since many GST inducers prevent rodent chemical carcinogenesis, potential chemopreventive agents have been screened by their induction capabilities. However, reliable markers useful to predict results of prospective chemopreventive trials in populations are not established. Immunohistochemical studies have revealed that many cancers, histologically classified as adenocarcinomas or squamous cell carcinomas, express GST P1-1. Its expression is regulated at transcriptional level and regulatory elements of the gene have been clarified. However, transacting factors responsible for expression in cancer tissues remain to be clarified. In addition, stability of GST P1 mRNA is suggested to be partly responsible in some cell lines. Plasma or serum GST P1-1 levels are increased in 30-50% of patients with cancers of the gastrointestinal tract. This form is also suggested to participate in resistance to anticancer drugs such as cisplatin and daunorubicin, and its expression in cancer tissues may be of prognostic value in cancer patients. Further studies on this enzyme family are clearly needed to obtain a better understanding of cancer prevention and therapy.