An Abnormality in the p53 Pathway following γ-Irradiation in Many Wild-Type p53 Human Melanoma Lines
作者： Dominic A. Scudiero , Stephen H. Friend , Albert J. Fornace , Qimin Zhan , M. Saeed Sheikh
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摘要: Abstract DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53, and, in turn, p53 transactivates a number of downstream effector genes GADD45, CIP1/WAF1 , and MDM2 . The induction these following IR appears to be strictly dependent upon presence wild-type functional known evoke G 1 arrest. In this study, we characterized 56 cell lines from 9 different types with predetermined genotype by measuring relative mRNA levels after IR. A higher fraction melanoma had (wt) (5/8, or 63%) compared nonmelanoma (11/48, 23%). Most wt (nonmelanoma) (11/12, 92%) showed clear both GADD45 On other hand, many (4/5, 80%) normal but little no Despite defect induction, found that all exhibited strong arrest increased protein results demonstrated radiation-induced could occur p53- pathway without appreciable lines. Time course experiments prolonged induced expression transcripts which was lacking, suggesting some sort compensatory mechanism involving defective induction. We reproduce effect RKO colon carcinoma cells blocked constitutive antisense vectors. These findings reveal is common human
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