ErbB4/HER4: role in mammary gland development, differentiation and growth inhibition.
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.
Muraoka-Cook
Rebecca S
RS
UNC-Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, 450 West Ave CB 7295, Chapel Hill, NC 27599, USA.
Feng
Shu-Mang
SM
Strunk
Karen E
KE
Earp
H Shelton
HS
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
D014408:Biomarkers, Tumor; D006131:Growth Inhibitors; D020033:Protein Isoforms; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4