Akt isoform-specific inhibition of MDA-MB-231 cell proliferation

Cell Signal. 2011 Jan;23(1):19-26. doi: 10.1016/j.cellsig.2010.07.016. Epub 2010 Aug 2.

Abstract

To dissect the isoform-specific roles of Akt in breast cancer cells, constitutively active Akt isoforms were introduced into MDA-MB-231 cells. Both Akt1 and Akt2 efficiently inhibited the growth of MDA-MB-231 cells. Overexpression of Akt1 down-regulated ERK activity inhibiting Ser 259 phosphorylation of c-Raf and subsequent downstream signaling. Akt2 overexpression up-regulated the cell cycle inhibitor p27. Cycloheximide decay assays showed that Akt2 increased the stability and nuclear localization of p27, thus inhibiting the cyclin E/CDK2 complex. These results suggest that the inhibition of cell proliferation by Akt1 and Akt2 is mediated by isoform-specific mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Phosphorylation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-raf / metabolism
  • Signal Transduction

Substances

  • Cyclin E
  • Protein Isoforms
  • Cyclin-Dependent Kinase Inhibitor p27
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Extracellular Signal-Regulated MAP Kinases