GRB7 is required for triple-negative breast cancer cell invasion and survival

Breast Cancer Res Treat. 2012 Jun;133(2):607-15. doi: 10.1007/s10549-011-1822-6. Epub 2011 Oct 18.

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease that is usually associated with poor prognosis, and frequently associated with the basal-like breast cancer gene expression profile. There are no targeted therapeutic modalities for this disease, and no useful biomarkers. High GRB7 RNA expression levels are associated with an elevated risk of recurrence in patients with operable TNBC treated with standard adjuvant anthracycline and taxane therapy. To determine whether GRB7 is involved in the pathobiology of TNBC, we evaluated the biological effects of GRB7 inhibition in a panel of triple-negative cell lines-MDA-MB-468, MDA-MB-231, HCC70, and T4-2. We found GRB7 inhibition reduced cell motility and invasion of these cell lines and promoted cell death by apoptosis in 3D culture. These data suggest that GRB7 itself, or GRB7-dependent pathways, may prove to be important therapeutic targets in this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Female
  • GRB7 Adaptor Protein / antagonists & inhibitors
  • GRB7 Adaptor Protein / genetics
  • GRB7 Adaptor Protein / physiology*
  • Humans
  • Neoplasm Invasiveness / genetics
  • Neoplasms, Basal Cell / genetics
  • Neoplasms, Basal Cell / pathology
  • Peptides, Cyclic / pharmacology
  • Receptor, ErbB-2 / deficiency
  • Receptors, Estrogen / deficiency
  • Receptors, Progesterone / deficiency
  • Reproducibility of Results

Substances

  • G7-18NATE
  • Peptides, Cyclic
  • Receptors, Estrogen
  • Receptors, Progesterone
  • GRB7 Adaptor Protein
  • Receptor, ErbB-2