title: ErbB2 is essential in the prevention of dilated cardiomyopathy.
abstract: Amplification of the gene encoding the ErbB2 (Her2/neu) receptor tyrosine kinase is critical for the progression of several forms of breast cancer. In a large-scale clinical trial, treatment with Herceptin (trastuzumab), a humanized blocking antibody against ErbB2, led to marked improvement in survival. However, cardiomyopathy was uncovered as a mitigating side effect, thereby suggesting an important role for ErbB2 signaling as a modifier of human heart failure. To investigate the physiological role of ErbB2 signaling in the adult heart, we generated mice with a ventricular-restricted deletion of Erbb2. These ErbB2-deficient conditional mutant mice were viable and displayed no overt phenotype. However, physiological analysis revealed the onset of multiple independent parameters of dilated cardiomyopathy, including chamber dilation, wall thinning and decreased contractility. Additionally, cardiomyocytes isolated from these conditional mutants were more susceptible to anthracycline toxicity. ErbB2 signaling in cardiomyocytes is therefore essential for the prevention of dilated cardiomyopathy.
authors: The Salk Institute, La Jolla, California, USA.
authors: Steven A
authors: SA
authors: Crone
authors: You-Yang
authors: YY
authors: Zhao
authors: Lian
authors: L
authors: Fan
authors: Yusu
authors: Y
authors: Gu
authors: Susumu
authors: S
authors: Minamisawa
authors: Yang
authors: Y
authors: Liu
authors: Kirk L
authors: KL
authors: Peterson
authors: Ju
authors: J
authors: Chen
authors: Ronald
authors: R
authors: Kahn
authors: Gianluigi
authors: G
authors: Condorelli
authors: John
authors: J
authors: Ross
authors: Kenneth R
authors: KR
authors: Chien
authors: Kuo-Fee
authors: KF
authors: Lee
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000517:prevention & control; D004317:Doxorubicin / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D020043:Genes, Essential; D018734:Genes, erbB-2; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D066247:Receptor, ErbB-4; D015398:Signal Transduction
chemical_list: D004317:Doxorubicin; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human; C587690:Erbb4 protein, mouse