Regulation of Sialomucin Complex Expression and Its Effect on HER Receptor Interaction
Abstract
Sialomucin complex (SMC) is a heterodimeric glycoprotein complex consisting of a mucin subunit ASGP-1 and a transmembrane subunit ASGP-2, which is highly overexpressed on the surface of ascites 13762 rat mammary adenocarcinoma cells. ASGP-2 appears to be a ligand for the growth factor receptor Erb(beta)-2. In normal rat mammary gland the levels of both SMC and Erb(beta)-2 are sharply increased during pregnancy, In normal cultured mammary epithelial cells (MEC) SMC is post- transcriptionally regulated by Matrigel and TGF(beta). SMC expression in the 13762 mammary adenocarcinoma cells is unaffected by Matrigel or TGF%. In contrast, ErbB2 is maximally expressed when MEC are embedded in Matrigel. Although SMC and Erb(beta)-2 can be found in a complex in whole lactating rat mammary tissue, the two proteins are more readily co- immunoprecipitated from freshly isolated MEC, whose polarity is disrupted as well as in the tumor, which also has its polarity disrupted. Finally, in tumor cell lines that overexpress SMC, antibody binding to Erb(beta)-2 is significantly reduced, while the overall levels of Erb(beta)-2 in the cells are not reduced. Thus, overexpression of SMC and formation of the SMC/Erb(beta)-2 complex may contnbute to increased metastatic potential and decreased responsiveness of some breast cancers to anti-Erb(beta)-2 therapeutic agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA405314
Entities
People
- Kermit Carraway
- Nebila Idris
Organizations
- University of Miami