GST-pi expression correlates with oxidative stress and apoptosis in breast cancer.
Glutathione S-transferase (GST) is known to play a key role in the detoxification and reduction of reactive oxygen species (ROS). Thus, we assessed GST activity and GST-pi expression in relation to oxidative stress and apoptosis in breast cancer. Tumor tissues from 32 breast cancer patients were evaluated for GST activity and thiobarbituric acid reactive substances (TBARS) that are by-products of oxidative stress. Four-micron sections of formalin-fixed, paraffin embedded tumors were stained immunohistochemically with anti-GST-pi. Apoptotic cells were detected by in situ end labeling of DNA fragments using a commercial kit. TBARS levels were significantly higher in breast cancers of older patients. GST-pi expression was up-regulated in breast cancers that exhibited higher oxidative stress and associated with higher GST activity. Apoptosis in GST-pi negative tumors was not correlated with GST activity, but GST-pi positive tumors within the same range of oxidative stress showed a reduction in apoptosis as well as an increased GST activity. This correlation was absent in GST-pi positive tumors experiencing higher oxidative stress. GST-pi expression may influence the level of GST activity and delay apoptosis in breast cancer. However, GST-pi expression in tumors with higher levels of oxidative stress may not be sufficient to abrogate the deleterious effects of ROS.
Huang
Jingxiang
J
Department of Anatomy, Faculty of Medicine, National University of Singapore, S117597, Singapore.
Tan
Puay Hoon
PH
Tan
Benny Kwong Huat
BK
Bay
Boon Huat
BH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000473:pathology; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D018384:Oxidative Stress; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D007527:Isoenzymes; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017392:Thiobarbituric Acid Reactive Substances; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase