Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin.

TLDR

Polymorphic epithelial mucin (PEM) is a developmentally regulated cell‑surface protein in mammary cells, aberrantly expressed in tumors, and contains variable tandem repeats that present tumor‑associated epitopes recognized by monoclonal antibodies. The full PEM sequence was deduced from cDNA and shows a protein with an N‑terminal signal peptide, a central tandem repeat domain, and a C‑terminal transmembrane segment with a cytoplasmic tail, containing many potential O‑glycosylation sites. The complete PEM sequence reveals that length variations in the tandem repeat region create a variable number tandem repeat locus.

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.