Transforming growth factor beta 1 as a biomarker for prostate cancer.

Abstract

Using the mouse prostate reconstitution (MPR) model system, under conditions where the ras and myc oncogenes are introduced via a recombinant retrovirus into both the mesenchymal and epithelial compartments of the urogenital sinus, poorly differentiated prostate cancer is produced with high frequency (> 90%) using inbred C57BL/6 mice. Northern blotting and immunohistochemical analysis showed that the transition from benign prostatic hyperplasia (BPH) to prostate cancer is invariably associated with the induction of elevated transforming growth factor-beta 1 (TGF-beta 1) expression. Similar analysis of TGF-beta 1 in human BPH and prostate cancer is consistent with our MPR results and indicates that the accumulation of extracellular TGF-beta 1 is significantly more intense in prostate cancer compared to normal or benign prostate tissues. Interestingly, where benign pathologies are observed in the prostatic stroma in the presence of benign prostatic epithelium, extracellular TGF-beta 1 is seen predominantly in the stromal compartment. Experimental studies clearly demonstrate that mRNA levels of TGF-beta 1 and other growth related genes are regulated by androgens in prostate cancer cells. Overall, our results suggest that elevated TGF-beta 1 is involved in the development of prostate cancer. Direct determination of TGF-beta 1 levels and distribution as well as analysis of localized and systemic effects produced by TGF-beta 1 may serve as useful biomarkers for prostate cancer.