Increase in CIP2A expression is associated with doxorubicin resistance

FEBS Lett. 2011 Mar 9;585(5):755-60. doi: 10.1016/j.febslet.2011.01.018. Epub 2011 Jan 18.

Abstract

The cancerous inhibitor of protein phosphatase 2A (CIP2A) increases the migration and metastasis of various cancer cells. Overexpression of CIP2A has been shown to increase the proliferation of MDA-MB-231 cells. We thus assessed whether CIP2A expression is associated with sensitivity to doxorubicin. MDA-MB-231 cells showed an increase in CIP2A expression after treatment with doxorubicin, while MCF-7 cells showed a decrease in CIP2A expression. The overexpression of CIP2A in MCF-7 cells overcame the inhibition of cell proliferation in response to doxorubicin treatment. CIP2A expression was not affected by wild-type or mutant p53. However, mutant p53 blocked doxorubicin-mediated CIP2A down-regulation in HCT116 cells. As a regulation mechanism of doxorubicin-mediated CIP2A expression, we showed that phosphorylated Akt was involved in the suppression of CIP2A expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutant Proteins / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Autoantigens
  • CIP2A protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mutant Proteins
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Proto-Oncogene Proteins c-akt