Wild-type function of the p53 tumor suppressor protein is not required for apoptosis of mouse hepatoma cells.
The role of the tumor suppressor protein p53 in apoptosis of mouse hepatoma cells was studied. Different lines were used which were either p53 wild-type or carried various types of heterozygous or homozygous p53 mutations. The presence of mutations was demonstrated to correlate with a lack in transactivating activity of p53. While UV-light effectively produced apoptosis in cells of all lines, irrespective of their p53 mutational status, gamma-irradiation induced the formation of micronuclei but failed to induce apoptosis. Both UV- and gamma-irradiation led to nuclear accumulation and increases in p53 protein in p53 wild-type cells. Similarly, no significant differences in apoptotic response between p53 wild-type and p53 mutated cells were seen with other apoptotic stimuli like CD95/APO-1/Fas or TNFalpha. These data suggest that wild-type p53 is not required for induction of apoptosis in mouse hepatoma cells which may explain the apparent lack of p53 mutations in mouse liver tumors.
Unger
C
C
Institute of Toxicology, University of Tübingen, Wilhelmstr. 56, 72074 Tübingen, Germany.
Buchmann
A
A
Bünemann
C L
CL
Kress
S
S
Schwarz
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular; D053938:DNA Fragmentation; D015972:Gene Expression Regulation, Neoplastic; D008099:Liver / Q000166:cytology; D051379:Mice; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000032:analysis / Q000235:genetics
C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor