Heregulin regulation of Akt/protein kinase B in breast cancer cells.
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.
Liu
W
W
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California, 94305, USA.
Li
J
J
Roth
R A
RA
D001943:Breast Neoplasms / Q000201:enzymology*; D002352:Carrier Proteins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000502:physiology; D015870:Gene Expression; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D020893:Receptor, ErbB-3; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D066246:ErbB Receptors; D006023:Glycoproteins; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C087230:heregulin beta1; C494918:AKT1 protein, human