Molecular cloning and expression of human Tumor-associated Polymorphic Epithelial Mucin

Gendler S. J, Imperial Cancer Research Fund
Lancaster C. A, Imperial Cancer Research Fund
Taylor Papadimitriou J, Imperial Cancer Research Fund
Duhig T, Imperial Cancer Research Fund
Peat N, Imperial Cancer Research Fund
Burchell J, Imperial Cancer Research Fund
Pemberton L, Imperial Cancer Research Fund
El-Nasir Lalani, Aga Khan University
Wilson D, Imperial Cancer Research Fund

Abstract

Human mammary cells present on the cell surface a polymorphic epithelial mucin (PEM) which is developmentally regulated and aberrantly expressed in tumors. PEM carries tumor-associated epitopes recognized by the monoclonal antibodies HMFG-1, HMFG-2, and SM-3. Previously isolated partial cDNA clones revealed that the core protein contained a large domain consisting of variable numbers of 20-amino acid repeat units. We now report the full sequence for PEM, as deduced from cDNA sequences. The encoded protein consists of three distinct regions: the amino terminus consisting of a putative signal peptide and degenerate repeats; the major portion of the protein which is the tandem repeat region; the carboxyl terminus consisting of degenerate tandem repeats and a unique sequence containing a transmembrane sequence and a cytoplasmic tail. Potential O-glycosylation sites (serines or threonines) make up more than one-fourth of the amino acids. Length variations in the tandem repeat result in PEM being an expressed variable number tandem repeat locus. Tandem repeats appear to be a general characteristic of mucin core proteins.