Progression and Metastasis of Mammary Carcinomas: Potential Role of the Mucl Glycoprotein.
Abstract
MUC 1 is a heavily glycosylated transmembrane mucin glycoprotein that is highly expressed and aberrantly glycosylated by >92% of primary and metastatic breast cancers. It is hypothesized that expression of the MUC1 protein may confer an advantage to tumor cells, perhaps by modulating the adhesive properties and/or by modulating the cells' immunogenicity. We have mutated the mouse Muc-1 locus using homologous recombination. Analysis of more than 400 offspring of mice heterozygous for the mutation revealed that 25% of the mice are homozygous and lack expression of Muc-1 RNA and protein. There was no obvious pathology of the tissues of mutant mice nor any obvious developmental abnormalities. To investigate the role of Muc-1 in the progression and metastasis of mammary tumors, mice homozygous for the mutated Muc-1 gene were mated with mice containing the Polyoma Virus Middle T antigen transgene driven by the MM%%IV promoter (Guy et. al., 1992b). Primary tumor growth was significantly slower in Muc-1 deficient mice than in the control animals. There was a trend towards decreased numbers of mice with lung metastases in Muc-1 mutant mice. These data directly demonstrate for the first time that the Muc-1 molecule plays a significant role in the growth of mammary tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 29, 1995
- Accession Number
- ADA300026
Entities
People
- Gerald J. Rowse