title: ErbB4/HER4: role in mammary gland development, differentiation and growth inhibition.
abstract: The ErbB receptor tyrosine kinase family has often been associated with increased growth of breast epithelial cells, as well as malignant transformation and progression. In contrast, ErbB4/HER4 exhibits unique attributes from a two step proteolytic cleavage which releases an 80 kilodalton, nuclear localizing, tyrosine kinase to a signal transduction mechanism that slows growth and stimulates differentiation of breast cells. This review provides an overview of ErbB4/HER4 in growth and differentiation of the mammary epithelium, including its physiologic role in development, the contrasting growth inhibition/tumor suppression and growth acceleration of distinct ErbB4/HER4 isoforms and a description of the unique cell cycle regulated pattern of nuclear HER4 ubiquitination and destruction.
authors.affiliation: UNC-Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, 450 West Ave CB 7295, Chapel Hill, NC 27599, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Muraoka-Cook
authors.forename: Shu-Mang
authors.initials: SM
authors.lastname: Feng
authors.forename: Karen E
authors.initials: KE
authors.lastname: Strunk
authors.forename: H Shelton
authors.initials: HS
authors.lastname: Earp
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D002454:Cell Differentiation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D020033:Protein Isoforms; D066247:Receptor, ErbB-4; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D006131:Growth Inhibitors; D020033:Protein Isoforms; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4