Differential regulation of p73 variants in response to cisplatin treatment in SH-SY5Y neuroblastoma cells

Int J Oncol. 2006 Jul;29(1):147-54.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Neuroblastoma
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • 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
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • GADD45A protein, human
  • Nuclear Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Small Interfering
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cisplatin