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Int J Oncol ; 29(1): 147-54, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16773194

ABSTRACT

The present study aims to investigate the role of p73 in response to cisplatin treatment in p53 wild-type neuroblastoma SH-SY5Y cells. Results showed that cisplatin induced a dose-dependent up-regulation of p53, p73, and a number of p53-responsive genes. Interestingly, endogenous Deltaexon2p73-expression was down-regulated by cisplatin treatment. Neither p21 nor GADD45 induction was observed in p53-deficient Lan-1 cells, although endogenous TAp73 expression was markedly induced. In the presence of cisplatin, exogenous TAp73 overexpression in SH-SY5Y cells induced p21 up-regulation without altering the apoptotic sub-G1 cell population. Moreover, siRNA-mediated suppression of TAp73 expression did not alter the sub-G1 population. Collectively, our results suggest that wt-p53 SH-SY5Y cells respond to cisplatin by inducing p73 isoform regulation and sustaining p53-dependent apoptosis that is independent of TAp73alpha.


Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Nuclear Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Alternative Splicing , Apoptosis , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , DNA-Binding Proteins/genetics , Dose-Response Relationship, Drug , Humans , Neuroblastoma , Nuclear Proteins/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA Interference , RNA Stability , RNA, Messenger/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Time Factors , Transfection , Tumor Protein p73 , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/genetics
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