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Hepatocarcinoma-specific Mutant p53-249ser Induces Mitotic Activity but Has No Effect on Transforming Growth Factor ß1-mediated Apoptosis¹

Laboratoire d'Oncologie Moléculaire, INSERM CJF9302 [F. P., A. P., A. P. M., M. O.], Unité de Pathologie Ultrastructurale [E. T.], and Unité de Cytologie Analytique [J. P. M., B. F.], CJF 9302 Centre Léon Bérard, 28, rue Laennec, 69008 Lyon, France; Institut fur Tumorbiologie, Krebsforschung der Universitat Wien, Wien, Austria [G. F., F. O.]; and Laboratoire d'Hématologie, Hôpital Charles Nicolle, Rouen, France [T. F.]

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 ArgSer) 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 ß1-mediated apoptotic death of Hep3B cells which is not affected by the expression of p53-249ser.

¹ This work was supported by grants from Comité Départemental de l'Ain de La Ligue de Lutte Contre le Cancer, and the NIH (CA-54567). F. P. was supported by fellowships from the Institut de Formation Superieure Biomedicale and La Ligue National de Lutte Contre le Cancer.

² To whom requests for reprints should be addressed.

Received 12/17/93. Accepted 3/ 4/94.

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