The glutathione-related detoxification system is increased in human breast cancer in correlation with clinical and histopathological features.
OBJECTIVE
The glutathione detoxification pathway includes glutathione S-transferase (GST) and peroxidase (GPX) isoenzymes as well as glutathione reductase (GSSR). Though well established from cultured cancer cell lines, its involvement in resistance is still unclear in the tumours. This study aimed to describe the parameters that influence the glutathione contents and associated activities in breast cancer.


METHODS
The components of the glutathione pathway were measured in the tumours from 41 women with primary breast cancer in comparison with those in the matched tumour-free samples. Appropriate statistical studies (regression analysis, Wilcoxon signed rank test) explored the influence of clinical and prognostic factors.


RESULTS
Reduced and total glutathione contents were largely increased (P < 0.0001) and all related activities were significantly enhanced in the tumours. Interindividual variations were described, probably due to various parameters (age, menopause, axillary lymph node status, S and G2 + M cell fractions, ER, cathepsin-D and c-ErbB-2 expressions) that influence particular components of the glutathione pathway, especially the glutathione levels.


CONCLUSIONS
The breast tumours improved their redox status and detoxification capacities depending on various parameters of significance for cell proliferation and aggressiveness, which supports the involvement of the glutathione pathway in malignant cell resistance to oxidative stress and apoptosis.
Perquin
M
M
Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, UFR SciFA, Université de Metz, Campus Bridoux, Rue Claude Bernard, 57070 Metz, France.
Oster
T
T
Maul
A
A
Froment
N
N
Untereiner
M
M
Bagrel
D
D
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008593:Menopause; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis
D002402:Cathepsin D; D005978:Glutathione; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen