Involvement of p53 and WAF1/CIP1 in gamma-irradiation-induced apoptosis of retinoblastoma cells.
Retinoblastoma is an intraocular malignancy of childhood, which is very radiosensitive. gamma-irradiation, however, induces side effects, and the precise mechanisms of tumor cell death after the treatment remain unknown. In this study, we demonstrated that gamma-irradiation induced apoptosis (programmed cell death) in human retinoblastoma cell lines Y79 and WERI-Rb-1. The expression levels of p53, tumor suppressor gene product, and its-associated protein, WAF1/CIP1, were both up-regulated, and function of p53 was remarkably activated after the treatment. Moreover, apoptosis was induced in the absence of gamma-irradiation by overexpression of the WAF1/CIP1 gene in both retinoblastoma cells. These results indicate that the transfer of the WAF1/CIP1 gene may have potential for the treatment of human retinoblastomas instead of gamma-irradiation.
Kondo
Y
Y
Department of Neurosciences, Cleveland Clinic Foundation, Ohio 44195, USA.
Kondo
S
S
Liu
J
J
Haqqi
T
T
Barnett
G H
GH
Barna
B P
BP
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology / Q000528:radiation effects; D017930:Genes, Reporter; D006801:Humans; D019572:Retinal Neoplasms; D012175:Retinoblastoma; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase