MUCI Facilitation of Growth in Chemically Induced Mammary Gland Tumors in Muc-1 Mutant and MUCI Transgenic Mice
Abstract
Muci is a cell-associated mucin glycoprotein that is highly over-expressed in greater than 90% of mammary gland tumors. Our studies have focused on elucidating the effect of Muci on tumor development, metastasis, and immune function. Mud-deficient mice were bred with mice expressing the c-neu protooncogene under control of the MMTV promoter to generate spontaneous mammary tumors. These mice developed unifocal tumors between 7 and 18 months of age. Tumor onset, progression, metastasis, and immune function were analyzed in the Mud-deficient and Muc1-expressing mice. Tumors developed in 93% (51/55) Muci mice and in 91% (51/56) of Mud* mice. Age of tumor onset was seven weeks lower for mice lacking Muci, and these mice +1+ were 1.5-times as likely to have lung metastasis as Muci mice. We found that the immune system of the Mud-deficient mice was severely compromised, as both T cells and natural killer cells failed to be activated and dendritic cells were non-functional. Thus, the lack of Muci protein had a dramatic effect on tumor latency, metastasis and general immune competence. These results add a new dimension to the function of this important tumor antigen.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA387867
Entities
People
- Sandra Gendler