Relative activity and specificity of promoters from prostate-expressed genes

To evaluate their relative activity and specificity for prostate cells promoter and regulatory regions from three prostate-expressed genes-prostate-specific antigen (PSA), probasin, and relaxin H2-have been compared in prostate cell lines and in lines of breast, bladder, liver, kidney, lung, and ovarian origin.

After transfection into different cell types, the activity of promoters was assayed using linked reporter genes and normalized against that of the Rous sarcoma virus. Activity was measured both in the presence and in the absence of co-transfected androgen receptor (AR).

PSA and probasin regulatory regions showed strong responsiveness to co-transfection of the AR in most cell types. The core PSA promoter region showed low activity and specificity, but the specificity and level of expression were substantially increased by inclusion of upstream sequences, particularly the enhancer region. Probasin promoter fragments showed specificity of expression for prostate cell lines but required AR for significant levels of expression. Relaxin promoter fragments directed significant AR-inducible expression in prostate cells but showed little specificity and variable AR responsiveness in other cell types.

Of regulatory regions tested, a 430-base pair probasin promoter and PSA enhancer/core promoter showed the best combination of AR-stimulated prostate cell expression with limited expression in other cell types.