The Role of MUC1 Cytoplasmic Domain in Tumorigenesis
Annual summary rept. 1 May 2003-30 Apr 2004
MAYO CLINIC SCOTTSDALE AZ
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The overall aim of the research is to develop a better understanding of the role of MUCl in breast cancer. Loss of Muc1 mouse homologue of MUCl significantly reduces tumor progression in polyomavirus middle. T antigen PyV MT -induced mammary tumors. The high transforming activity of the PyV MT antigen depends on c-Src which has been shown to phosphorylate the cytoplasmic tail of MUC1. Our aim is to identify specific proteins that associate with MUCl and induce signaling that potentiates tumorigenesis, specifically the modulation of c-Src activity and signaling in MMTV-PyV MT tumorigenesis. We have found that MUCl and c-Src interact in pYV MT-induced mammary tumors. Our data provide insights into the possible mechanism for the significant delay in tumor progression that is observed in the absence of Mucl. We suggest that the interaction of Mucl with c-Src, a key player in PyV MT transformation, promotes the binding of c-Src to its downstream targets and influences its intracellular localization. Other studies in the lab have shown that overexpressed MUCl induces mammary gland tumors. We found that overexpressed MUCl also inhibits mammary gland involution. These results suggest that MUCl functions as a weak oncogene in the mammary gland.
- Medicine and Medical Research