Hepatocarcinoma-specific mutant p53-249ser induces mitotic activity but has no effect on transforming growth factor beta 1-mediated apoptosis.
Mutations affecting the p53 gene abrogate its tumor suppressor activity. It is, however, unclear whether such mutations can generate mutant p53 proteins with an intrinsic transforming ability. More importantly, the mechanism(s) by which they exert such activity is unknown. We report here that p53-deficient hepatoma cells (Hep3B) transfected with mutant p53-249ser (codon 249 Arg-->Ser) acquire a new phenotype with an increased in vitro survival and mitotic activity. However, such a phenotypic change is not sufficient to cause a major shift in the poor tumorigenic potential of these cells. This is apparently due to transforming growth factor beta 1-mediated apoptotic death of Hep3B cells which is not affected by the expression of p53-249ser.
Ponchel
F
F
Laboratoire d'Oncologie Moléculaire, INSERM CJF9302, Lyon, France.
Puisieux
A
A
Tabone
E
E
Michot
J P
JP
Fröschl
G
G
Morel
A P
AP
Frébourg
T
T
Fontanière
B
B
Oberhammer
F
F
Ozturk
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001120:Arginine; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers; D016158:Genes, p53; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000235:genetics*; D008940:Mitotic Index; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012694:Serine; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000633:toxicity*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016212:Transforming Growth Factor beta; D012694:Serine; D001120:Arginine