MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism.
beta-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 beta-catenin binding to MUC1 on downstream beta-catenin-dependent events. Compared with HEK293T cells transfected with empty vector or CD8 alone, expression of the MUC1 cytoplasmic tail inhibited beta-catenin binding to E-cadherin, decreased translocation of beta-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 beta-catenin/LEF-1/cyclin D1/c-Myc pathway.
Lillehoj
Erik P
EP
Department of Pediatrics, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 13-029, Baltimore, MD 21201, USA. elillehoj@peds.umaryland.edu
Lu
Wenju
W
Kiser
Timothy
T
Goldblum
Simeon E
SE
Kim
K Chul
KC
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014158:Transcription, Genetic; D051176:beta Catenin / Q000378:metabolism*
D000951:Antigens, Neoplasm; D016827:CD8 Antigens; D015820:Cadherins; D051821:Lymphoid Enhancer-Binding Factor 1; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D051176:beta Catenin; D019938:Cyclin D1