Molecular Basis of Prostate-Specific Androgen-Independent Expression of a Homeobox Gene
Abstract
Hox genes encode the transcriptional regulatory proteins that are largely responsible for establishing the body plan of all metazoan organisms. A subset of Hox genes continues to be expressed during the period of organogenesis and into adulthood. Hoxb-13 is a member of the Hox gene family that is expressed in the spinal cord, hindgut, and urogenital sinus during embryogenesis. We have characterized its expression in adult mouse tissues and have found that it is expressed in only two sites: the prostate gland and the distal colon. Surprisingly, accumulation of Hoxb-13 mRNA is not diminished in prostate glands following castration indicating that its expression is androgen independent. In support of this suggestion, we have also demonstrated that the human Hoxb-13 gene is expressed in androgen-independent PC-3 cells, as well as androgen starved LNOaP cells. Stimulation of LNOaP cells with androgen does not alter the expression of Hoxb-13. In our application, we proposed to characterize the molecular basis of prostate specificity and androgen independence of the Hoxb- 13 gene with a view towards developing new treatments for advanced prostate cancer. These elements would provide a unique reagent that could be incorporated into gene therapy strategies to treat advanced prostate cancer in patients that have undergone androgen deprivation therapy. Currently available prostate-specific regulatory elements are all androgen dependent and would be unlikely to function well in these patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2002
- Accession Number
- ADB283513
Entities
People
- Charles J Bieberich
Organizations
- University of Baltimore