Role of the POZ-ZF Transcription Factor Kaiso in Breast Cell Proliferation and Tumorigenesis; Annual summary rept. 9 Mar 2005-8 Mar 2008

摘要

Kaiso is a member of the POZ-ZF family of transcription factors, first identified as a binding partner for the p120ctn cell adhesion co-factor. Previous work in our laboratory showed that Kaiso was misexpressed in approximately 40% of human breast tumors and we also identified cyclin D1 as a putative Kaiso target gene. This project elucidated the mechanism by which Kaiso regulates cyclin D1 expression and the effects of this on breast cell tumorigenesis. Using minimal promoter assays, electrophoretic mobility shift assays and immunoblotting we showed how Kaiso regulates cyclin D1 expression. Our work to date demonstrates that Kaiso regulates cyclin D1 transcription through its binding properties (by binding to both sequence specific TCCTGCNA and methylated CpG sites within the promoter). We also demonstrated that Kaiso and p120ctn can modulate canonical Wnt signaling and activation of cyclin D1.