| First Author | Li Y | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 4 | Pages | e19102 |
| PubMed ID | 21533058 | Mgi Jnum | J:172397 |
| Mgi Id | MGI:5007595 | Doi | 10.1371/journal.pone.0019102 |
| Citation | Li Y, et al. (2011) The Cytoplasmic Domain of MUC1 Induces Hyperplasia in the Mammary Gland and Correlates with Nuclear Accumulation of beta-Catenin. PLoS One 6(4):e19102 |
| abstractText | MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD), the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to beta-catenin and protecting beta-catenin from GSK3beta-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of beta-catenin, which is associated with a significant increase of beta-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with beta-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer. |
