Progression and Metastasis of Mammary Carcinomas: Potential Role of the Mucl Glycoprotein.
Annual rept. 1 Aug 94-31 Jul 95,
MAYO FOUNDATION ROCHESTER MN
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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 andor 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 MMIV 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.
- Medicine and Medical Research