MUC1 Functions as an Oncogene by Targeting the Nucleus of Human Breast Cancer Cells
Annual rept. 1 Sep 2004-31 Aug 2005
DANA-FARBER CANCER INST BOSTON MA
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The MUC1 oncoprotein is aberrantly overexpressed in 80-90 of human breast carcinomas. Little, however, is known about the role of MUC1 in the development of breast cancer. The Specific Aims of this Idea Award are To determine if MUC1 overexpression is sufficient to induce transformation and To assess whether MUC1 localizes to the nucleus and thereby regulates gene expression. Work supported by this Award has demonstrated that-the MUC1 -cytoplasmic domain MUC1-CD is sufficient to induce transformation and that the oncogenic effects of MUC1 are mediated at least in part by stabilization-of the Wnt effector Beta-catenin. our work has also shown that MUC1-interacts with the p53 tumor suppressor and contributes to the regulation of p53-dependent transcription. More recent studies show that MUC1 binds to estrogen receptor alpha ERa and that MUC1 increases ERa levels by blocking its ubiquitination and degradation. MUC1 occupies the promoters of estrogen responsive genes and activates ERa-mediated transcription. These findings indicate that MUC1 induces transformation, localizes to the nucleus and regulates gene expression in breast cancer cells.
- Medicine and Medical Research