Alterations of Glutathione and GSTM1 Mutation Induce Tumor Metastasis and Invasion Via EMT Pathway in Breast Cancer Patients

Abstract

Objectives: Alteration in the Glutathione (GSH) and Glutathione S-Transferase (GST) family lead to various disorders including breast cancer. However, the role of GSH and GSTM1 in the onset of breast cancer is still not fully elucidated. In the present study we observed considerable deficiency in the levels of glutathione and genetic mutation in the GSTM1 enzyme that influence susceptibility to breast cancer metastasis and invasion via EMT pathway. Methods: GSTM1 genotype was identified by multiplex polymerase chain reaction (PCR), real time (RT)-PCR and western blotting in breast tumor samples and adjacent normal control tissue (ANCT) samples. The endogenous glutathione levels were determined by high performance liquid chromatography (HPLC).The tumor metastasis, invasion and epithelial-mesenchymal transition (EMT) biomarkers were determined by RT-PCR. Results: In present study genotyping analysis of GST investigated that genetic mutation in GSTM1 was detected in breast cancer tissue samples. mRNA and protein expression of GSTM1 was significantly downregulated in tumor samples as compared to adjacent normal control tissue (ANCT) samples in breast cancer patients. Significant reduction of total glutathione (GSHt P<0.05) was observed among correlation with patient ages, stages and histological grades of breast cancer patients. Additionally, downregulation of GSTM1 promotes EMT pathway that leads to enhanced the expression of tumor proliferation, invasion and metastasis in breast cancer patients (p<0.05). Conclusion: The present findings suggest that GSTM1 genotype could be a potential biomarker for breast cancer pathogenesis. Keywords: Breast cancer, Glutathione, Glutathione S-Transferase M1, Invasion, Metastasis, Proliferation