title: [Antiproliferative effect of bcl-2 gene does not concern the control of mitotic events].
abstract: E1A + c-Ha-ras-transformants overexpressing bcl-2 oncogene are able to be arrested at the G1/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 kinases (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-ras 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.
authors.affiliation: Institute of Cytology RAS, St. Petersburg. annanelioudova@hotmail.com
authors.forename: A M
authors.initials: AM
authors.lastname: Neliudova
authors.forename: A I
authors.initials: AI
authors.lastname: Brichkina
authors.forename: M P
authors.initials: MP
authors.lastname: Rukhlova
authors.forename: N D
authors.initials: ND
authors.lastname: Aksenov
authors.forename: T V
authors.initials: TV
authors.lastname: Pospelova
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division; D002461:Cell Line, Transformed; D003470:Culture Media; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase; D016195:G2 Phase; D019254:Genes, bcl-2 / Q000502:physiology*; D011905:Genes, ras; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D011123:Polyploidy; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077546:Roscovitine
chemical_list: D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D003470:Culture Media; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases; D015739:Nocodazole