ANTIPROLIFERATIVE EFFECT OF bcl-2 GENE DOES NOT CONCERN THE CONTROL OF MITOTIC
EVENTS
A. M. Nelyudova,1 A. I. Brichkina, M. P. Rukhlova, N. D. Aksenov, T. V. Pospelova
Institute of Cytology RAS, St. Petersburg Russia;
1 e-mail: annanelioudova@hotmail.com
E1A+c-Ha-ras-transformants overexpressing bcl-2 oncogene are able to be arrested at the Gi/S boundary of the
cell cycle after DNA damage and upon serum starvation, this cell cycle blockage being accompanied by a decrease in the activity of cyclin
E-Cdk2 complexes. Roscovitine-induced inhibition of cyclin-dependent kina-ses (Cdks) activity does not result in the G1/S
arrest of E1A+c-Ha-ras+bcl-2-transformants. Roscovitine treatment causes an accumulation of G2/M cells, mainly at the
expense of mitotic cells. However, the expression of Bcl-2 oncoproducts does not re-establish the regulation of mitotic events broken
by introduction of E1A and c-Ha-ms oncogenes in normal cells, as revealed by the treatment of E1A+c-Ha-ras+bcl-2-transformants with
nocodazole inducing mitotic arrest in normal cells. In spite of the elevated expression of antiapoptotic bcl-2 gene in transformants,
nocodazole treatment results in mass apoptotic death preceded by polyploidy. Roscovitine also induces apoptosis with no polyploid cell
accumulation being observed. Inhibition of Cdks activity with Roscovitine, as well as violation of microtubule depolymerization with
nocodazole result in the apoptotic death in the tested cell lines sensitive (E1A+c-Ha-ras) and resistant (E1A+c-Ha-ras+bcl-2) to damaging
agents. Thus, the application of Roscovitine, a specific inhibitor of Cdks, suggests that the decrease in Cdks activity in
E1A+c-Ha-ras+bcl-2-transformants is not likely to be responsible for G1/S cell cycle arrest realization after damaging
influences. Moreover, an antiproliferative effect of Bcl-2 in E1A+c-Ha-ras-transformants is restricted by restoration of cell cycle events at
G1/S and G2/M boundaries, and does not concern the program of mitotic events regulation.
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