Journal
CANCER LETTERS
Volume 232, Issue 2, Pages 279-288Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2005.02.043
Keywords
apoptosis; Bcl-XL; mammary carcinoma; p53; ras; transgenic rat
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Seven mammary carcinoma cell lines were established from 7,12-dimethylbenz[a]anthracene-induced tumors developed in a human c-Ha-ras transgenic rat. Without apoptotic stimuli, a large amount of p53 protein was detected in the C11 cell line (C11). whereas all cell lines expressed variable levels of the assayed death receptor/ligand, bcl-2 family and p53 cascade-related genes. The p53 gene in C11 had a mutation at codon 246, in the DNA-binding region of p53. Transcriptional activity of the mutant protein appeared to be lower than that of the wild-type p53. Despite the presence of p53 mutation, C11 was more sensitive to apoptosis triggered by etoposide, paclitaxel and staurosporine than the cell lines expressing wild-type p53. These data Suggest that the apoptosis induced by intracellular injury occurs via the transcriptionally impaired mutant p53 in C11. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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