Abstract
β-Catenin binds to the cytoplasmic region of the type 1 membrane glycoprotein MUC1. In the current study, we utilized HEK293T cells expressing the full-length MUC1 protein, or a CD8/MUC1 fusion protein containing only the MUC1 cytoplasmic tail, to investigate the effects of β-catenin binding to MUC1 on downstream β-catenin-dependent events. Compared with HEK293T cells transfected with empty vector or CD8 alone, expression of the MUC1 cytoplasmic tail inhibited β-catenin binding to E-cadherin, decreased translocation of β-catenin into the nucleus, reduced activation of the LEF-1 transcription factor, and blocked expression of the cyclin D1 and c-Myc proteins. Furthermore, expression of MUC1 was associated with decreased cell proliferation, either in the context of the transfected HEK293T cells, or when comparing wild type (Muc1+/+) vs. knockout (Muc1-/-) mouse primary tracheal epithelial cells. We conclude that MUC1 inhibits cell proliferation through a β-catenin/LEF-1/cyclin D1/c-Myc pathway.
Original language | English (US) |
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Pages (from-to) | 1028-1038 |
Number of pages | 11 |
Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
Volume | 1773 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2007 |
Externally published | Yes |
Keywords
- Cancer
- Cyclin D1
- Cytoplasm
- E-cadherin
- LEF-1
- Membrane
- Nucleus
- Reepithelialization
- Transcription
- c-Myc
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology