title: Formation of MUC1 metabolic complex is conserved in tumor-derived and normal epithelial cells.
abstract: MUC1 is abundantly expressed at the surface of epithelial cells in many tissues and their carcinomas. In humans, genetic polymorphism and differential splicing produce isoforms that may contribute to MUC1 participation in protection of the cell surface, modulation of cell-cell interactions, signaling, and metastasis. Biosynthetic and processing studies in tumor-derived cell lines indicate that cell surface MUC1 consists of a non-covalently associated heterodimer of separate cytoplasmic tail and extracellular domains. This heterodimer results from a single precursor proteolytically cleaved intracellularly. To determine whether similar processing of this isoform occurs in normal epithelial cells, we have examined cell-associated MUC1 and MUC1 released into medium by normal human uterine, mammary, and prostate epithelial cells. Cell-associated MUC1/REP was extracted as an SDS labile complex which was resistant to dissociation by boiling, urea, sulfhydryl reduction, peroxide, high salt, or low pH and was present in all normal cells examined. Addition of various proteolytic inhibitors during extraction had no effect on the proportion of this complex detected. MUC1 released into the medium was not associated with a particulate fraction (100,000g insoluble) and lacked the cytoplasmic tail. MUC1/REP and the MUC1 isoform lacking the transmembrane/cytoplasmic tail region, MUC1/SEC, mRNA were detected in all normal cells examined indicating that both shed and secreted MUC1 are likely to contribute to soluble forms found in culture media.
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE 19707, USA
authors.forename: JoAnne
authors.initials: J
authors.lastname: Julian
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Carson
mesh_terms: D017398:Alternative Splicing; D019921:Biotinylation; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D018396:Mucin-1 / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011233:Precipitin Tests; D011467:Prostate / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014599:Uterus / Q000378:metabolism
chemical_list: C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments; D020033:Protein Isoforms; D012333:RNA, Messenger; D012313:RNA