Work

MUC-1 mucin assays for monitoring therapy in metastatic breast cancer

Year: 1998

Type: article

Abstract: MUCl mucin is an integral membrane glycoprotein expressed by most if not all ‘wet’ epithelia, such as on bladder, breast, gastric, pancreas, ovary and respiratory tract epithelium, with a molecular weight varying between 250 and 1000 kD. Its extracellular domain consists of a heavily O-link glycosylated peptide core made up in the main of a variable number of multiple repeats of a 20 amino acid sequence referred to as the variable number tandem repeat (VNTR) domain with each VNTR having five potential Olinkage sites. Glycosylation is under enzymatic control and occurs post-translationally and sequentially, leading potentially to the production of four sugar core types capable of elongation into polysaccharide chains. Alterations to these enzymes and to enzymes involved in post-translational modification, which can be associated with disease, will obviously affect the glycosylation state of MUCl. In general, the polysaccharide side chains of tumour associated MUCl are shorter than those on the normally expressed molecule. Both aberrant and up-regulated expression of MUCl are features of malignancy. It is apparent, therefore, that MUCl is highly heterogeneous owing to its polymorphic nature (the VNTRs) and the high degree of variation in glycosylation (for reviews see’.‘). In normal breast tissue, MUCl is expressed on the apical surface of epithelial cells in the ducts and acini from where the molecule is shed via milk fat globules and in soluble form into the milk.3 In tumours, cell polarization is lost, and as a consequence, MUCl has the potential to be expressed over the whole cell surface. This altered cell surface expression, coupled with the disruption of the normal tissue archi-

Source: The Breast

DOI: 10.1016/s0960-9776(98)90105-9

Authors: R. Graves, J. Hilgers, H. Fritsche, D. Hayes, J.F.R. Robertson