GST isoenzymes in matched normal and neoplastic breast tissue

Abstract

The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression.The interindividual variation in the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and of 1,2-epoxy-3-(p-nitrophenoxy) propane (EPNP) with glutathione (GSH) by cytosolic glutathione S-transferases (GSTs) were investigated in human breast matched normal and tumor samples. The GSTA, GSTM, GSTP and GSTT isoenzymes from the crude extracts of matched breast normal and tumor tissues in terms of their immunological properties using western blotting were compared.In most of the samples, the GST activities were higher in the tumor than in the normal cytosolic fractions against both CDNB and EPNP. In the western blotting analysis, it was proved statistically that in normal and tumor epithelial cells, there was difference between GST pi and theta isoenzymes expressions (p<0.05), but no difference between the staining scores of GST mu and alpha isoenzymes (p>0.05). In normal epithelium there was a stronger GST theta expression than in invasive tumor tissues (p=0.013). However, the stronger GST pi expression was observed in tumor epithelium than in normal epithelium in human breast cancers (p=0.000). We found the GSTP protein level and GST activities were higher in the breast tumor than in the normal cytosolic fractions against both CDNB and EPNP, thus implicating a certain biological importance.

Glutathione Transferases: Potential Targets to Overcome Chemoresistance in Solid Tumors

“…This variability is even more potentiated in cancer cells [29]. In general, GSTP1 over-expression seems to be a hallmark of proliferating cells in many solid tumors, including transitional cell carcinoma of urinary bladder [30,31], renal cell carcinoma [32,33], ovarian cancer [34,35], breast cancer [36,37] and colorectal cancer [38,39]. Regarding other GST classes, increased expression of GSTA1 is confirmed in colorectal cancer [39], GSTO1-1 is upregulated in transitional cell carcinoma [40], esophageal squamous cell carcinoma [41], pancreatic cancer [42], and breast cancer [43], while GSTM1 overexpression is observed in transitional cell carcinoma of urinary bladder [31], renal cell carcinoma [33] and breast cancer [44].…”

Molecular evaluation of glutathione S transferase family genes in patients with sporadic colorectal cancer

“…In general, GSTP1 appears to be highly expressed in proliferating cells compared with differentiated cells. In addition, many of the GSTs are overexpressed in various neoplastic cells and higher levels are observed in aggressive cancer cells[ 15 ]. The change in the GSTP1 gene also significantly alters the enzymatic activity[ 16 , 17 ], influencing the detoxification of carcinogens, causing DNA damage, and exerting an indirect effect on the risk of cancer development[ 18 ].…”

Glutathione S-transferase enzyme activity and protein expression in patients with recurrent tonsillitis and idiopathic tonsillar hypertrophy

“…Both forms of antioxidants (enzymatic or non-enzymatic) have the ability to protect cells from oxidative stress and the produced materials. Infections are also responsible for increased free radicals levels in tissues 11,12,15 . In this condition, cells responsible for inflammation such as macrophages, neutrophils, eosinophils, and monocytes produce free radicals to defend against bacteria or viruses.…”

“…GST activities were determined spectrophotometrically as described by Habig et al (1974). This is based on monitoring thioether formation in the reaction medium at 340 nm using CDNB as substrate 15 . This method has been modified for the ELISA microplate reader system 16 .…”