Isolation of Target Genes for NKX3.1 in Prostate Carcinogenesis
Annual Summary rept. 1 Mar 2003-29 Feb 2004
UNIVERSITY OF MEDICINE AND DENTISTRY OFNEW JERSEY PISCATAWAY
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Nkx3.l 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.l mutant mouse model relative to normal prostate epithelium. Our findings suggest that Nkx3.l loss-of-function leads to a deregulated secretory function of prostate which representing a defect differentiation of prostate epithelium, thus may contribute to the increased susceptible to carcinogenesis. Moreover, Nkx3.l 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 role of Nkx3.l in advanced stages of prostate cancer progression, gene expression profiling has been performed using Nkx3.l Pten double mutant and Nkx3.lptenp27exp kiPl triple mutant prostatic lesions. Our preliminary data have shown that Nkx3.l loss-of-function cooperates with heterozygosity of p27exp kiPl in promotion of prostate carcinogenesis through up-regulation of cyclin Dl. Our findings provide insight into the roles of Nkx3.l, by itself or in cooperation with other broad-spectrum tumor suppressors, in prostate carcinogenesis.
- Medicine and Medical Research