Abstract
The mucin gene, Muc-1, encodes a high molecular weight integral membrane glycoprotein that is present on the apical surface of most simple secretory epithelial cells. Muc-1 is highly expressed and aberrantly glycosylated by most carcinomas and metastatic lesions. Numerous functions have been proposed for this molecule, including protection of the epithelial cell surface, an involvement in epithelial organogenesis, and a role in tumor progression. Mice deficient in Muc-1 were generated using homologous recombination in embryonic stem cells. These mice appeared to develop normally and were healthy and fertile. However, the growth rate of primary breast tumors induced by polyoma middle T antigen was found to be significantly slower in Muc-1 deficient mice. This suggests that Muc-1 plays an important role in the progression of mammary carcinoma.
Highlights
The MUC1 protein is a heavily glycosylated cell-associated mucin glycoprotein that is highly expressed and aberrantly glycosylated by the majority of carcinomas and, in particular, by Ͼ92% of primary and metastatic breast cancers
We constructed a replacement-type targeting vector, 129Muc-1GT, in which the Muc-1 gene was disrupted by the insertion of a cassette containing the E. coli -galactosidase (LacZ) gene [33] and SV40 poly(A) sequence in addition to the phosphoglycerate kinase (PGK) neo gene (Figs. 1 and 2A)
A Screen for Potential Compensating Genes—We explored the possibility that the up-regulation of expression of one or more mucin-like genes or membrane glycoproteins may have accounted for the apparent lack of a phenotype in Muc-1-deficient mice
Summary
The MUC1 protein is a heavily glycosylated cell-associated mucin glycoprotein that is highly expressed and aberrantly glycosylated by the majority of carcinomas and, in particular, by Ͼ92% of primary and metastatic breast cancers. Isolation of the mouse Muc-1 gene indicated that the most strongly conserved regions corresponded to the serine, threonine, and proline residues within the repeat domain and to the transmembrane and cytoplasmic domains [13, 14]. This would suggest that the primary function of the repeat domain is to act as a scaffold for carbohydrate attachment. The pattern of Muc-1 expression in the adult mouse and in mouse mammary carcinomas correlated well with the pattern of expression observed for the human MUC1 gene [17, 18]
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