Investigation of the Role of Sialomucin Complex (SMC)/Muc4, a Unique Intramembranous HER-2/ErbB-2 Ligand as a Suppressor of Apoptosis
Annual summary rept. 1 Apr 2003-31 Mar 2004
MIAMI UNIV FL SCHOOL OF MEDICINE
Pagination or Media Count:
Muc4sialomucin complex SMC is a high Mr heterodimeric glycoprotein complex which was originally observed at the cell surfaces of 13762 rat mammary adenocarcinoma cells and has been more recently found in many accessible and vulnerable epithelia. It is composed of a mucin subunit ASGP-1 and a transmembrane subunit ASGP-2. The latter has two EGF-like domains and can form intramembrane ligand-receptor-type complexes with the receptor tyrosine kinase ErbB2. An important aspect of SMCMuc4 is its ability to repress apoptosis when transfected into tumor cells. Our hypothesis is that SMCMuc4 is multifunctional. It acts as an epithelial protective agent by forming a steric barrier at epithelial apical surfaces and by contributing to signaling through ErbB2 involved in epithelial differentiation and repression of apoptosis. Both of these functions may contribute to tumor progression when Muc4SMC is inappropriately overexpressed.
- Anatomy and Physiology
- Medicine and Medical Research