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Gottschalk, B; Klein, A.
Restoration of wild-type p53 in drug-resistant mouse breast cancer cells leads to differential gene expression, but is not sufficient to overcome the malignant phenotype.
Mol Cell Biochem. 2013; 379(1-2): 213-227. Doi: 10.1007/s11010-013-1643-5
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Führende Autor*innen der Med Uni Graz
Gottschalk Benjamin
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Abstract:
We established a breast cancer cell line from a fast growing mouse WAP-SVT/t breast tumor. Cells from this line, SVTneg2, switched off T-antigen expression, carry a missense mutation at the p53 codon 242 (mouse G242 corresponds to human hot spot mutation G245), are malignantly transformed, highly aneuploid and very insensitive to apoptotic stimuli. To examine the influence of wild-type p53 (wtp53) restoration on the behavior of the SVTneg2 cells, we transfected these cells with wtp53 and generated three permanent cell lines expressing wtp53. Interestingly, restoration of p53 had no influence on chemotherapy sensitivity and the transformation capacity of these breast cancer cells, but markedly changed the gene expression of wtp53-dependent genes after doxorubicin treatment. We postulate that restoration of p53 leads to massive changes in gene expression and to a reduced proliferation rate, but is not sufficient to overcome the malignant phenotype and the chemoresistance of SVTneg2.
Find related publications in this database (using NLM MeSH Indexing)
Aneuploidy -
Animals -
Antibiotics, Antineoplastic - pharmacology
Base Sequence -
Binding Sites -
Cell Line, Tumor - drug effects
Cell Proliferation -
Consensus Sequence -
Doxorubicin - pharmacology
Drug Resistance, Neoplasm -
Female -
Gene Expression -
Gene Expression Regulation, Neoplastic -
Mammary Neoplasms, Experimental - drug therapy Mammary Neoplasms, Experimental - metabolism Mammary Neoplasms, Experimental - pathology
Mice -
Phenotype -
Protein Binding -
Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism

Find related publications in this database (Keywords)
Trp53
p53 restoration
Aneuploidy
Chemoresistance
Breast cancer
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