Heregulin regulation of Akt/protein kinase B in breast cancer cells

Biochem Biophys Res Commun. 1999 Aug 11;261(3):897-903. doi: 10.1006/bbrc.1999.1144.

Abstract

In the present studies, we demonstrate that heregulin is a potent and rapid activator of the serine/threonine kinase called Akt in the MCF-7 breast cancer cell line but not in 3 other breast cancer cell lines (T47D, HBL-100, and MDA-231). The extent of activation of Akt in the 4 cell lines correlated with the ability of heregulin to activate phosphatidylinositol 3-kinase and inhibition of the kinase blocked Akt activation. A monoclonal antibody to HER2 inhibited the ability of heregulin to activate Akt in the MCF-7 cells. BT474, a breast cancer cell line which overexpresses HER2, had high basal Akt enzymatic activity. This high basal activity was lowered when cells were pre-incubated with an anti-HER2 monoclonal antibody which is used to treat breast cancer patients. Our results indicate that heregulin is a potent activator of Akt and that overexpression of HER2 in breast cancers could also lead to activation of Akt.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / enzymology*
  • Carrier Proteins / pharmacology*
  • Enzyme Activation / drug effects
  • ErbB Receptors / physiology
  • Gene Expression
  • Glycoproteins / pharmacology*
  • Humans
  • Neuregulin-1*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / physiology
  • Receptor, ErbB-3
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Glycoproteins
  • Neuregulin-1
  • Proto-Oncogene Proteins
  • heregulin beta1
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt