Glutathione transferase and mammary tumors
Abstract
The analysis of publications from the last 5 years is presented in this review. These articles describe the relationship of glutathione transferase (GST) with mammary tumors. Most of these works are dedicated to investigating the genotypic relationship between GST and neoplasms in human. The most common are single nucleotide polymorphism of GSTP1 Val105Ile (rs1695) and gene deletions GSTM1 and GSTT1. Several publications describe polymorphisms of GSTM3(rs4970737), GSTM4 and GSTA5. These polymorphisms (especially GSTP1 Val105Ile) are associated with the risk of mammary tumors, overall survival and relapse in patients of some ethnic groups. This is as a result of reduced enzymatic activity of GST and disturb of ability to detoxify substrates. Some studies demonstrate that single nucleotide polymorphism of GSTP1 Val105IIe is associated with a better response to chemotherapy and overall survival of patients, but no association with genotypes of GSTM1 and GSTT1. The injections of carcinogenic compounds into the tissue of mammary gland or its feeding to rats leed to decrease of GST activity and to development of tumors. The increased expression of GST in breast cancer cell lines leeds to increase of the resistance of these cells against various chemical compounds therefore the enzyme catalyzes the binding of these compounds to glutathione and this prevent their negative effects and is necessary for the formation of conjugates. Such increased expression of GST indicates on the resistance of breast cancer cell lines in particular to the action of drugs, which reduces their therapeutic effect. This is shown on cell lines BT474, MCF-7, MCF-7/ADR, MCF-7/ADR-1024, MCF-10A, MDA-MB-231, MDA-MB-468 and T47D. Chemical compounds (including antitumor drugs), that reduce the activity and/or expression of GST, can have a cytotoxic effect on these cells. Mammary tumors associated with epigenetic changes that do not change the sequence of nucleotides in GST genes. The methylation of the GSTP1 promoter decreases an expression of protein in mammary tissue and increases a risk of cancer in different ethnic groups. Compounds increase the level of expression of genes when they are able to lower the level of methylation or to affect demethylation. Polymorphisms of GST genes, their association with response to chemotherapy and overall survival of patients, expression of GST and it dependence on the action of anticancer drugs, methylation of GST promoter are associated with diagnosis, prognosis, and treatment of mammary neoplasms.
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