Role of Nkx3.1 Homeodomain Protein in Prostate Carcinogenesis and Differentiation
Abstract
Prostate cancer is a significant health problem in aging American men. Approximately 350,000 American men were diagnosed and 42,000 deaths were attributed to prostate cancer in 1998. Despite identification of chromosomal regions of instability that are associated with prostate cancer, there are an undetermined series of molecular events that lead to de-differentiation of prostatic epithelial cells and ultimately to prostate carcinoma. The specific genes responsible for neoplastic transformation of the prostate are largely unknown. Nkx3.1 is a homeodomain transcription factor that is expressed in an androgen-dependent and largely prostate specific manner. The Nkx3.1 gene localizes to the chromosomal region 8p21, a region that is often deleted in human prostate cancers. The goals of this study are to overexpress Nkx3.1 in vitro and determine the effects on growth/differentiation, patterns of target gene expression and tumorigenicity of prostate carcinoma cell lines. Expression patterns of Nkx3.1 in human prostate tumor specimens will be examined immunohistochemically, and microdissected prostate tumor samples will be used to search for Nkx3.1 mutations and/or evidence of hypermethylation. Specific cell types and androgen-dependent expression patterns of Nkx3.1 will also be monitored immunohistochemically in mouse prostates. Overall, our work will determine whether loss of Nkx3.1 function is a major cause of prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2000
- Accession Number
- ADA385631
Entities
People
- Jeffrey D. Milbrandt
Organizations
- Washington University in St. Louis