Phase I NKX3.1 in Prostate
Abstract
We have isolated a prostate-specific gene, NKX3.1, that maps to chromosome 8p21, a common region for loss of heterozygosity in human prostate cancer. NKX3.1 is a homeobox gene that is expressed at high levels in adult human prostate. Deletion of NKX3.1 in the mouse has suggested that NKX3.1 has a suppressor effect on prostatic epithelial cell growth, and that haploinsufficiency is sufficient to produce epithelial hyperplasia. Inconsistent with the interpretation that NKX3.1 is a classical tumor suppressor gene, the coding region of NKX3.1 is not mutated in human prostate cancer. We have generated an antibody highly specific for NKX3.1. Using this reagent we have shown that loss of NKX3.1 expression is increasingly likely with prostate tumor progression. This loss of expression ranges from 16% of radical prostatectomy specimens to 80% in metastases. We have shown that a genetic polymorphism (NKX3.1 R52C) that changes DNA-binding properties of the NKX3.1 protein is present in approximately 10% of the human population. We have not found a difference in the frequency of NKX3.1 R52C between Caucasians and African Americans. The polymorphism is a risk factor for aggressive prostate cancer (high grade or high stage) (RR=1.8, 95%CI = 1.01-3.22).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2001
- Accession Number
- ADA390414
Entities
People
- Edward P. Gelmann
Organizations
- Georgetown University