Effects of enhancing p21(waf1) on proliferation and expression of G1 cyclins and CDKs in human breast cancer cells

The cyclin-dependent kinase inhibitor p21( waf1/cipl/sdil) is an important negative regulator in control of cell cycle. Its functions of inhibiting ca ncer cell growth and its effects on expression of G1 phase cyclins and rela ted CDKs are a worthy topic for study. The plasmid expressing p21 with high level was transformed to human breast cancer cells, and the expression of p21 in cells was enhanced, then the cell growth rate, anchorage- independen t growth and tumorigenecity were tested, at the same time the expression le vels of cyclinD1, CDK4, cyclinE and CDK2 were analyzed by Northern blot. Th e results showed that since the expression of p21 was enhanced in the cell, the rate of cell growth and anchorage-independent growth was inhibited, tu morigenecity was suppressed, the level of expression of cyclinE and CDK2 de creased while that of cyclinD1 and CDK4 was not affected. It is suggested t hat the enhanced expression of p21 markedly inhibits the proliferation and lessens the tumorigenecity of breast cancer cells, and that p21 expression is not related to that of cyclinD1 and CDK4, but affects the expression of cyclinE and CDK2.