Accession Number : ADA300026

Title :   Progression and Metastasis of Mammary Carcinomas: Potential Role of the Mucl Glycoprotein.

Descriptive Note : Annual rept. 1 Aug 94-31 Jul 95,

Corporate Author : MAYO FOUNDATION ROCHESTER MN

Personal Author(s) : Rowse, Gerald J.

PDF Url : ADA300026

Report Date : 29 AUG 1995

Pagination or Media Count : 21

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.

Descriptors :   *GLYCOPROTEINS, *CELLS(BIOLOGY), *CANCER, *MAMMARY GLANDS, *METASTASIS, CELLS, GROWTH(GENERAL), PROTEINS, ADHESION, NEOPLASMS, MUTATIONS, LUNG, PATHOLOGY, MICE, NUMBERS, VIRUSES, ANTIGENS, ABNORMALITIES, LABORATORY ANIMALS, IMMUNOGENS.

Subject Categories : Medicine and Medical Research
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE