siRNA-mediated down-regulation of iASPP promotes apoptosis induced by etoposide and daunorubicin in leukemia cells expressing wild-type p53

Leuk Res. 2009 Sep;33(9):1243-8. doi: 10.1016/j.leukres.2009.02.016. Epub 2009 Mar 18.

Abstract

Oncoprotein inhibitory member of the ASPP family (iASPP) is a key inhibitor of tumor suppressor p53. Our previous study revealed that the expression of iASPP in acute leukemia (AL) patients was higher than that of normal control which implied that iASPP might play an important role in the pathogenesis and/or disease progression of AL. In this study, the iASPP expression was blocked by RNA interference (RNAi) in two leukemic cell lines, Nalm6 and K562, to explore the effects of iASPP on leukemia cells. The results indicated that down-regulation of endogenous iASPP increased p53-dependent apoptosis of leukemia cells. Thus, iASPP could be a molecular target in leukemia therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Base Sequence
  • Cell Division / genetics
  • Cell Line, Tumor
  • DNA Primers
  • Daunorubicin / pharmacology*
  • Down-Regulation*
  • Etoposide / pharmacology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukemia / metabolism
  • Leukemia / pathology*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics*
  • Repressor Proteins
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents
  • DNA Primers
  • Intracellular Signaling Peptides and Proteins
  • PPP1R13L protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • Etoposide
  • Daunorubicin