title: Mutant p53 protein expression and antioxidant status deficiency in breast cancer.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, "Vinca" Institute of Nuclear Sciences, Mihaila Petrovica Alasa 12-14, University of Belgrade, 11 001 Belgrade, Serbia.
authors.forename: Zorka
authors.initials: Z
authors.lastname: Milicevic
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, "Vinca" Institute of Nuclear Sciences, Mihaila Petrovica Alasa 12-14, University of Belgrade, 11 001 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Kasapovic
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, "Vinca" Institute of Nuclear Sciences, Mihaila Petrovica Alasa 12-14, University of Belgrade, 11 001 Belgrade, Serbia.
authors.forename: Ljubica
authors.initials: L
authors.lastname: Gavrilovic
authors.affiliation: National Center of Cancer Research (NCRC), Institute for Oncology and Radiology of Serbia, Pasterova 14, 11 000 Belgrade, Serbia.
authors.forename: Zorka
authors.initials: Z
authors.lastname: Milovanovic
authors.affiliation: Department for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, Mihaila Petrovica Alasa 12-14, University of Belgrade, 11 001 Belgrade, Serbia.
authors.forename: Vladan
authors.initials: V
authors.lastname: Bajic
authors.affiliation: Department of Biology and Human Genetics, Institute of Physiology, Faculty of Pharmacy, Vojvode Stepe 450, University of Belgrade, 11 000 Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Spremo-Potparevic
keywords: antioxidants; breast carcinoma; lipid peroxidation; p53