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Sustained Accumulation of the Mitotic Cyclins and Tyrosine-phosphorylated p34^cdc2 in Human G₁-S-arrested Cancer Cells but not Untransformed Cells¹

Unité Mixte de Recherche 146 du Centre National de la Recherche Scientifique, Institut Curie-Recherche, Centre Universitaire, 91405 Orsay Cédex, France

Coupling mitosis to the completion of DNA replication in cycling embryonic extracts from Xenopus eggs appears to rely onblocking the activation of the tyrosine-phosphorylated p34^cdc2/cyclin B, which continues to build up when S phase is inhibited by adding unreplicated DNA (Smythe, C., and Newport, J. W., Cell, 68: 787–797, 1992). We show here that a similar mechanism might be operative in human tumor-derived cells, which, during a thymidine-aphidicolin block, stop progressing through S phase and thereby fail to undergo mitosis. Under such conditions, indeed, cancer cells do continue to accumulate cyclin A, cyclin B1, and tyrosine-phosphorylated p34^cdc2 to supranormal levels, a phenomenon that does not occur in untransformed, nonimmortalized human fibroblasts. Thus, in human cancer cells, the onset of active accumulation of cyclin A and cyclin B1 can be uncoupled from transit through the G₁-S and S-G₂ borders, respectively, and, as in simple embryonic cell cycles, the coupling of mitosis to the completion of S phase presumably relies, at least in part, on the prevention of premature activation of the tyrosine-phosphorylated p34^cdc2/cyclin B1 complex.

¹ This work was supported by the Centre National pour la Recherche Scientifique, the Curie Institute, and the Association pour la Recherche sur le Cancer, France.

² To whom requests for reprints should be addressed, at the CURIE Institute-Recherche, Bâtiment 110, Centre Universitaire, 91405 Orsay Cédex, France.

Received 7/ 7/97. Accepted 8/28/97.

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