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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.
Insights
The PUM gene locus codes for mucin-type glycoproteins found in various tissues and bodily fluids. This locus is a hypervariable minisatellite region of DNA that is transcribed and translated, with its polymorphism evident in the gene product.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- A single autosomal gene locus, PUM, encodes mucin-type glycoproteins identified initially in human urine.
- These glycoproteins are also present in epithelial tissues, bodily fluids like milk, and epithelial-origin tumors.
- Mucin-type glycoproteins are highly immunogenic, prompting research into epithelial-specific or tumor-associated antigens.
Purpose of the Study:
- To investigate the expression of PUM-coded mucins in normal and malignant cells.
- To characterize the PUM locus and its expressed gene product.
- To confirm the relationship between DNA polymorphism and protein polymorphism.
Main Methods:
- Isolation of complementary DNA (cDNA) coding for mammary mucin.
- Analysis of PUM locus using isolated cDNA.
- SDS-gel electrophoresis to separate glycoproteins.
- Immunohistology to assess antibody specificity.
Main Results:
- The PUM locus is a hypervariable minisatellite region of human DNA.
- This minisatellite region is unique as it is transcribed and translated into glycoproteins.
- The polymorphism within the PUM minisatellite DNA is also detectable in the expressed gene product (mucin-type glycoproteins).
- Numerous antibodies binding PUM-coded mucins exhibit tumor specificity.
Conclusions:
- The PUM locus represents a novel, transcribed, and translated hypervariable minisatellite region.
- The demonstrated polymorphism in both DNA and protein products has implications for cancer research.
- PUM-coded mucins and their associated antibodies are valuable tools for cancer diagnosis and potentially therapy.