Signaling molecules implicated in heregulin induction of growth arrest and apoptosis

Oncology Reports
F K Guerra-VladusicRuth Lupu

Abstract

Heregulin (HRG) is one of the groups of polypeptide growth factors that activate the erbB-2 receptor via induction of heterodimerization with erbB-3 and erbB-4 receptors. The biological effects of HRG have been extensively studied. The vast majority of the reports indicate that HRG induces cell growth in breast cancer cells expressing normal levels of erbB-2 and growth inhibition and apoptosis in cells over-expressing erbB-2. However, the mechanism by which HRG promotes cell growth inhibition and apoptosis is still unknown. Previously we reported that constitutive expression of HRG in an erbB-2-overexpressing cell line (SKBr-3) induced growth arrest and apoptosis. We also demonstrated that constitutive expression of HRG promoted a marked morphological change, G2/M delay of the cell cycle, and DNA fragmentation. In this study, we demonstrate the mechanism by which HRG induces these cellular effects. The doubling time of the SK/HRG cells increased in relation to the level of HRG expression, and the level of HRG expression dictates the morphological change of the cells as well as their ability to grow or not grow in an anchorage-independent manner. We demonstrate that these effects are accompanied by downregulation of both erbB-2 ...Continue Reading

Citations

Jul 16, 2004·Journal of Cellular Physiology·Patrizia CasaliniSylvie Ménard
Dec 17, 2008·Biochemical and Biophysical Research Communications·Thomas A MillerDouglas B Sawyer

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