Hrc. Kim et al., LEVELS OF P21(WAF1 CIP1) DO NOT AFFECT RADIATION-INDUCED CELL-DEATH IN HUMAN BREAST EPITHELIAL-CELLS/, International journal of oncology, 11(6), 1997, pp. 1349-1353
Loss of the wild-type p53 activity and/or overexpression of the proto-
oncogene bcl-2 are frequently detected in breast cancer and suggested
to be related to chemotherapy and radiation therapy resistance. To ide
ntify the downstream signaling molecules for anti-proliferative and ap
optotic activities of p53 and to investigate the interaction of bcl-2
with p53 in human breast epithelial cells, we have used the MCF10A cel
l line. We previously showed that overexpression of bcl-2 downregulate
s expression of p21(WAF1/CIP1) (a cyclin dependent kinase inhibitor wh
ich mediates p53 dependent G(1) arrest) and suppresses DNA damage-indu
ced apoptosis in MCF10A cells. In the present study, we constitutively
overexpressed p21(WAF1/CIP1) in bcl-2 overexpressing MCF10A cells to
determine whether downregulation of p21(WAF1/CIP1) is necessary for th
e anti apoptotic activity of bcl-2, and to investigate the roles of p2
1(WAF1/CIP1) in p53-mediated cell death upon irradiation. Overexpressi
on of p21(WAF1/CIP1) resulted in growth inhibition, but had no effect
on bcl-2 inhibition of apoptosis following irradiation. Also, overexpr
ession of p21(WAF1/CIP1) did not affect the dose-dependent radiation-i
nduced cell lethality as determined by a clonogenic survival assay. Th
ese results suggest that bcl-2 downregulation of p21(WAF1/CIP1) is ind
ependent of the anti-apoptotic activity of bcl-2, and that p21(WAF/CIP
1) is not involved in the p53-mediated cell death pathway.