Establishment of an apoptosis-sensitive rat mammary carcinoma cell line with a mutation in the DNA-binding region of p53.
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.
Hamaguchi
Tetsuya
T
Second Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-0001, Japan.
Matsuoka
Yoichiro
Y
Bechberger
John
J
Ohnishi
Takamasa
T
Fujita
Ken-ichi
K
Naus
Christian C
CC
Kusunoki
Masato
M
Tsubura
Airo
A
Tsuda
Hiroyuki
H
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D005260:Female; D011905:Genes, ras; D006801:Humans; D020935:MAP Kinase Signaling System; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494813:Bcl2l1 protein, rat; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D004247:DNA