GROWTH-FACTOR INVOLVEMENT IN PROGRESSION OF PROSTATE-CANCER

Understanding how the regulation of growth factor pathways alters duri ng prostate cancer (PC) progression may enable researchers to develop targeted therapeutic strategies for advanced disease. PC progression i nvolves the shifting of cells from androgen-dependent growth to an and rogen-independent state, sometimes with the loss or mutation of the an drogen receptors in PC cells. Both autocrine and paracrine pathways ar e up-regulated in androgen-independent tumors and may replace androgen s as primary growth stimulatory factors in cancer progression. Our dis cussion focuses on growth factor families that maintain homeostasis be tween epithelial and stromal cells in the normal prostate and that und ergo changes as PC progresses, often making stromal cells redundant. T hese growth factors include fibroblast growth factor, insulin-like gro wth factors, epidermal growth factor, transforming growth factor alpha , retinoic acid, vitamin D-3, and the transforming growth factor beta families. We review their role in normal prostate development and in c ancer progression, using evidence from clinical specimens and models o f PC cell growth.