Roles of the Mitotic Checkpoint Regulators Pin1 and Pin2 in Breast Cancer
Abstract
Our laboratory has recently identified a new protein, Pin1, that is involved in checkpoint control. Pin1 interacts with mitotic phosphoproteins and helps to orchestrate the timing of mitotic events. We found that Pinl is highly overexpressed in breast cancer. Pinl levels correlate with the levels of cyclin Dl protein as well as with cyclin Dl mRNA levels in human breast tumors. We have shown that Pin1 is a transcriptional activator of cyclin Dl. Activation occurs indirectly through the binding of phosphorylated c-jun. Our data indicate that Pinl may contribute to neoplastic transformation by causing accumulation of cyclin Dl. In addition, Pin1 contributes to cyclin Dl overexpression by regulating the turnover and subcellular localization of beta-catenin and inhibiting its interaction with APC. In Pin1 knock-out mice, mammary epithelial cells fail to undergo the usual proliferative burst during pregnancy, a phenotype that is very similar to the cyclin Dl knock-out. Finally, the PIN1 gene itself is an E2F target gene and essential for Neu/Ras induced transformation of mammary epithelial cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA412714
Entities
People
- Gerburg M Wulf
- Kun P. Lu
Organizations
- Beth Israel Deaconess Medical Center