Erbin-regulated sensitivity of MCF-7 breast cancer cells to TRAIL via ErbB2/AKT/NF-kappaB pathway

J Biochem. 2008 Jun;143(6):793-801. doi: 10.1093/jb/mvn032. Epub 2008 Mar 3.

Abstract

We have reported that Erbin expression was down-regulated in the Jurkat leukaemia T lymphocytes treated with the recombinant soluble tumour necrosis factor-related apoptosis-inducing ligand (rsTRAIL). Herein, we studied the expression and the regulation of Erbin and its binding partner, ErbB2, in the MCF-7 breast cancer cell line. We showed that the expressions of Erbin and ErbB2 were modulated by PKCdelta inhibitor, rottlerin, in the TRAIL-resistant MCF-7 cell line. The affinity of Erbin-ErbB2 interaction was reduced by ErbB2 phosphorylation. Inhibiting the expression of Erbin facilitated the sensitivity of the MCF-7 cells to TRAIL via suppressing the ErbB2/AKT/NF-kappaB signalling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / pharmacology*
  • Apoptosis / physiology
  • Benzopyrans / pharmacology
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Caspases
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • I-kappa B Kinase / metabolism
  • Immunoblotting
  • Immunoprecipitation
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / pharmacology
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction*
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*

Substances

  • Acetophenones
  • Adaptor Proteins, Signal Transducing
  • Benzopyrans
  • ERBIN protein, human
  • Enzyme Inhibitors
  • NF-kappa B
  • RNA, Small Interfering
  • TNF-Related Apoptosis-Inducing Ligand
  • rottlerin
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt
  • I-kappa B Kinase
  • Caspases