title: Levels of p21(WAF1/CIP1) do not affect radiation-induced cell death in human breast epithelial cells.
abstract: 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 identify the downstream signaling molecules for anti-proliferative and apoptotic activities of p53 and to investigate the interaction of bcl-2 with p53 in human breast epithelial cells, we have used the MCF10A cell line. We previously showed that overexpression of bcl-2 downregulates expression of p21(WAF1/CIP1) (a cyclin dependent kinase inhibitor which mediates p53 dependent G(1) arrest) and suppresses DNA damage-induced 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 the anti apoptotic activity of bcl-2, and to investigate the roles of p21(WAF1/CIP1) in p53-mediated cell death upon irradiation. Overexpression of p21(WAF1/CIP1) resulted in growth inhibition, but had no effect on bcl-2 inhibition of apoptosis following irradiation. Also, overexpression of p21(WAF1/CIP1) did not affect the dose-dependent radiation-induced cell lethality as determined by a clonogenic survival assay. These results suggest that bcl-2 downregulation of p21(WAF1/CIP1) is independent of the anti-apoptotic activity of bcl-2, and that p21(WAF/CIP1) is not involved in the p53-mediated cell death pathway.
authors.affiliation: WAYNE STATE UNIV,SCH MED,DEPT RADIAT ONCOL,DETROIT,MI 48201. KARMANOS CANC INST,DETROIT,MI 48201. VET ADM MED CTR,DEPT RADIAT ONCOL,DETROIT,MI 48201. WILLIAM BEAUMONT HOSP,DEPT RADIAT ONCOL,ROYAL OAK,MI 48073.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Rahman
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Waid
authors.forename: Y
authors.initials: Y
authors.lastname: Lee