Isolating of Target Genes for NKX3.1 in Prostate Carcinogenesis
Abstract
Nkx3.1 is a prostatic-specific tumor suppressor whose loss-of-function represents a critical step in prostate cancer initiation. However, the molecular basis is still largely unknown. We have been utilizing microarray analysis to pursue the gene expression profiling of prostatic lesions in the Nkx3.1 mutant mouse model relative to normal prostate epithelium. Our findings suggest that Nkx3.1 loss-of-function leads to deregulated secretory function of prostate which representing a defect differentiation of prostate epithelium, thus may contribute to the increased susceptible to carcinogenesis. Moreover, Nkx3.1 mutant prostates are deficient for anti-oxidative protection as a consequence of aging, which underlies its role in cancer predisposition. In an effort to explore the molecular alterations in advanced stages of prostate cancer progression, we find that the mutant mice share many features in common with human prostate cancer, including over-expression of various putative markers for human prostate cancer (e.g., Ezh2, Piml, Hepsin, and Clusterin). Furthermore, up-regulation of AP-1 components in androgen-independent tumor cells, as well as activation of cyclin D1 in the Nkx3.1;Pten;p27 compound heterozygous tumor cells, may reflect novel molecular pathways underlying prostate cancer progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA437384
Entities
People
- Xuesong Ouyang