It is well recognized that
cancers develop and grow as a result of disordered function of tumor suppressor genes and oncogenes, which may be exploited for screening purposes. Extensive evidence indicated
tumor suppressor protein p53 as candidate marker for mutation identification. We have investigated mutant p53
protein expression in human
breast tumors in relation to
antioxidant status deficiency. The study included 100
breast cancer patients. p53
protein expression was evaluated by Western blot assay and immunostaining using a CM-1, DO-7 and Pab240
antibodies.
Antioxidant parameters and lipid peroxidation were estimated by biochemical analyses. Western blotting with epitopespecific
monoclonal antibody Pab240 strongly suggests that nuclear extracts from
breast cancer cells express mutant forms of p53. It is of interest that the mutant forms of p53 overexpression in conjunction with the appearance of nuclear bodies are observed in highly aggressive
carcinomas. Expression of
isoform Δp53 (45 kDa) and
isoform of ~ 29 kDa were more common in cases with LN
metastasis. These studies point out the molecular consequences of oxidative stress (
lipid peroxides, LP, p<0.001) and
antioxidant status deficiency (
copper,
zinc superoxid dismutase, SOD, p<0.001;
catalase, CAT, p<0.01;
glutathione reductase,
GR, p<0.001;
glutathione, GSH, p<0.05) and indicate the importance of p53 mutation as the commonest genetic alteration detected in
breast cancer cells. The expression of mutant p53 is correlated to increased
lipid peroxides (0.346, p<0.05 ) and lowered
antioxidant activity of CAT (- 0.437, p<0.01) in the
breast cancer patients.