Muc1 Facilitation of Growth in Chemically Induced Mammary Gland Tumors in Muc1 Mutant and MUC1 Transgenic Mice

摘要

MUC1 is a cell-associated mucin glycoprotein that is highly over- expressed in greater than 90% of mammary gland carcinomas. Our hypothesis is that the high level of expression of MUCl in tumors facilitates tumor progression and metastasis. To generate spontaneously occurring tumors, we have mated mice carrying the unactivated c-neu protooncogene under control of the mouse mammary tumor virus (MMTVF) LTR with Muc1 wildtype (+/+) or knockout (-/-) mice. These mice develop mainly unifocal tumors at about 7 to 12 months of age. Surprisingly, age at the onset of tumor growth was significantly lower for the Muc1- deficient mice than for the wild type mice (p = 0.02 from two-sided, two- sample t-test (t=2.4, df = 34)). However, once tumors were palpable, the rate of tumor progression was similar in both groups. Mud-deficient mice are twice as likely to have lung metastasis than Muc1 +/+ mice (39% vs. 18%). We found that the immune system of the Muc1 -/- mice was severely compromised, as T cells showed virtually no proliferative response to Concanavalin A or T-cell receptor stimulation. Although data are incomplete at this time, Muc1 has a dramatic effect on tumor latency, metastasis and general immune competence.