HISTONE DEACETYLASE INHIBITOR STOPS PROLIFERATION OF CELLS TRANSFORMED
WITH ONCOGENES E1A AND cHA-RAS
M. V. Abramova,1 S. B. Svetlikova, N. D. Aksenov, T. V. Pospelova, V. A. Pospelov
Institute of Cytology RAS, St. Petersburg, Russia;
1 e-mail: mav@mail.cytspb.rssi.ru
Rat embryonic fibroblasts, transformed with E1A and cHa-ras oncogenes, are unable to stop in the cell cycle
checkpoints under growth factor withdrawal and genotoxic stresses (Bulavin et al., 1999). In the present paper, we showed that sodium
butyrate, an inhibitor of histone deacetyase activity, decreased the share of cells being in S-phase, and caused G1/S and
G2/M blocks of the cell cycle in the transformants. By means of RT-PCR and immunoblotting, we found that NaB significantly
changed the expression of genes involved in proliferation: cyclins D1, A, E and cyclin-dependent kinases Cdk2 and Cdk4, whereas the
amount of p21Waf1 and p27Kip1 inhibitors greatly increased. Along with accumulation of p21Waf1
protein content, that of Cdk2-bound p21 increases. Taken together, these data allow to suggest that NaB treatment does evidently restore
the capability of p21Waf1 to inhibit cyclin-kinase activity. One may suppose that inhibition of HDAC activity by sodium butyrate
leads to activation of yet unknown HDAC-dependent genes, which is followed by restoration of p21Waf1 function in spite of
the E1A oncogene expression.
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