The Role of Ubiquitin E3 Ligase SCFSKP2 in Prostate Cancer Development
Abstract
The CDK inhibitor p27Kipl acts as a negative regulator in the cell cycle and in prostate tumorigenesis. Either the loss of p27 or over-expression of its key regulator ubiquitin E3 ligase SKP2 is associated with prostate cancer. Prostate-sepcific expression of SKP2 is sufficient to induce hyperplasia, displasia, and low grade carcinoma in the mouse prostate gland. We propose to examine whether SKP2 cooperates with or is regulated by tumor suppressors such as Pten or Nkx3.1 implicated in prostatic tumorigenesis. In the past year, we have initiated the experiments by breeding and expansion of the colonies, crossing the SKP2 transgenic mice into Pten +/- strains, and ordering Nkx3.1 mice. Compound mice of SKP2 transgene and Pten +/- were made. Our initial studies suggest that there i&. no substantial difference in tumor frequency and grade in the SKP2 and Pten +/- compound mice versus single genetic alterations. These results suggest that PTEN may act through SKP2 for tumorigenesis. Since most of Pten null mice died early due to tumor growth in other tissues, we are in the process using Pten conditional knockout mice and prostate-specific-Cre recombinase to remove Pten in the prostate gland to determine the relationship between PTEN null and SKP2 expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA435854
Entities
People
- Hui Zhang
Organizations
- Yale University