Differential regulation of p73 variants in response to cisplatin treatment in SH-SY5Y neuroblastoma cells.
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.
Million
Karine
K
Centre National de Recherche Scientifique, Unité Mixte de Recherche 8126, Institut Gustave Roussy, Villejuif, France.
Horvilleur
Emilie
E
Goldschneider
David
D
Agina
Malik
M
Raguénez
Gilda
G
Tournier
Frédéric
F
Bénard
Jean
J
Douc-Rasy
Sétha
S
D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097642:GADD45 Proteins
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D002945:Cisplatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C493956:CDKN1A protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C000606460:TP73 protein, human