The human tumour-associated epithelial mucins are coded by an expressed hypervariable gene locus PUM

Abstract

A single highly-polymorphic autosomal gene locus PUM codes for a family of mucin-type glycoproteins, separable by SDS-gel electrophoresis, which we first identified in human urine. The locus also codes for glycoproteins which are abundant in several other normal epithelial tissues and body fluids, including milk, and in tumours of epithelial origin. These mucin-type glycoproteins seem to be very immunogenic in rodents and, in a search for epithelial specific or tumour-associated antigens, a large number of related antibodies have been isolated which bind to the PUM-coded mucins. Many of the antibodies show a pronounced tumour specificity on immunohistology and are being used widely in cancer diagnosis in vitro and in vivo and even in cancer therapy. To investigate the expression of these antigens in normal and malignant cells complementary DNA coding for the mammary mucin has been isolated. Here we present evidence obtained using this cDNA that the PUM locus is a hypervariable 'minisatellite' region of human DNA similar to those described by several groups, but which is novel in that it is transcribed and translated, and that the same polymorphism is demonstrable in the expressed gene product.

A 72 kD trophoblast glycoprotein defined by a monoclonal antibody

“…Solubilised StMPM protein fractionated over S200 Sephacryl in the presence of detergent. Fractionated 5T4 antigenicity assessed in ELISA family of mucin type glycoproteins (Swallow et al, 1987), but with clear differences from those defined by the CA or HMFG series of antigens (Wiseman et al, 1984;Burchell et al, 1983). These latter glycoproteins are defined by several monoclonal antibodies which have been shown to be reactive with a wide range of malignant tumour cells but also reactive with certain specialised normal epithelia.…”

Genetic regulation of MUC1 alternative splicing in human tissues

“…It has a centrally located tandem repeat (TR) domain (Lan et al, 1985;Gendler et al, 1987Gendler et al, , 1988Gendler et al, , 1990Swallow et al, 1987;Hareuveni et al, 1990) comprised of 20 -120 or more repeat units of 60 nucleotides, which encode 20 amino acids. The repeating units include several serine and threonine residues, which carry most of the glycosylation, and this glycosylation, as well as the general pattern of expression, is altered in cancerous cells (Taylor-Papadimitriou et al, 2002).…”

Polymorphic epithelial mucin from the sera of advanced breast cancer patients – isolation and partial characterisation

“…That the mucin was detectable in low levels in the pooled sera of normal individuals (Figure 2) In SDS polyacrylamide gels, PEM migrates as a series of bands differing slightly in electrophoretic mobility. This is due to the polymorphism which is seen at both the DNA and protein level (Swallow et al, 1987;Gendler et al, 1987). Each band represents one of several phenotypes which are the products of a number of codominant alleles present at a single gene locus.…”

“…Originally purified from human milk, this component has been termed PAS-O by Shimizu and Yamauchi (1982), EMA (epithelial membrane antigen) by Heyderman et al, (1979), by Hilkens et al (1984) and MSA (mammary serum antigen) by Stacker et al (1988). Karlsson et al (1983) first reported that the mucin exhibits a genetic polymorphism which was later shown to exist at both the protein and DNA level (Swallow et al, 1987;Gendler et al, 1987, respectively). Consequently, Gendler et al, (1988) have named the mucin polymorphic epithelial mucin, or PEM, a term which aptly describes its properties.…”