Role of Nkx3.1 Homeodomain Protein in Prostate Carcinogenesis and Differentiation
Abstract
Cancer of the prostate is the second most common cause of cancer morbidity and mortality in American males, currently accounting for ^30% of new cancer cases in this population. The chromosomal region most frequently involved in prostate cancer is located at 8p12-22 (3-5); indeed, a recent study showed that 63% of premalignant PIN foci have suffered chromosome deletions at this locus. One strong candidate for a gene involved in prostate cancer at this locus is the recently described Nkx3.1 gene, which encodes a homeodomain transcription factor. Studies of Nkx3.1-deficient mice have shown that the loss of a single allele is sufficient to promote hyperplasia in the prostate epithelium, indicating its potential role in prostate cancer initiation. To identify genes regulated by Nkx3.1, we have infected prostate carcinoma cells with adenovirus expressing Nkx3.1 and analyzed the changes in gene expression using microarray methodology. Immunohistochemistry using anti-Nkx3.1 antibodies was used to demonstrate that Nkx3.1 is expressed in luminal epithelial cells but not in basal, neuroendocrine or stromal cells. We examined Nkx3.1 expression in human prostate tumors and found that it was absent in the malignant cells in 60% of the tumor samples.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA398754
Entities
People
- Jeffrey Milbrandt
- John Svaren
- Rakesh Nagarajan
- Tim Fahrner
- Toshi Araki
Organizations
- Washington University in St. Louis