MUC1 Functions as a Oncogene by Targeting the Nucleus of Human Breast Cancer Cells

摘要

The MUC1 oncoprotein is aberrantly overexpressed in 80-90% of human breast carcinomas. Little, however, was known about the role of MUC1 in the development of breast cancer. The Specific Aims of this Idea Award were: (1) To determine if MUC1 overexpression issufficient to induce transformation; and (2) To assess whether MUC1 localizes to thenucleus and thereby regulates gene expression. Work supported by this Award hasdemonstrated that MUC1 induces transformation and that the cytoplasmic domain is sufficient for this function by stabilizing Beta-catenin (Task 1). Our results alsodemonstrate that the MUC1- C subunit is targeted to the nucleus where it interacts with p53, ERalpha and KLF4, and thereby regulates gene transcription in human breast cancer cells (Task 2). These findings have thus provided novel information that MUC1 induces transformation, localizes to the nucleus and regulates gene expression. The findings also indicate that overexpression of MUC1 by human breast tumors is of importance to the malignant phenotype and resistance to therapy.