Androgen receptor and growth factor signaling cross-talk in prostate cancer cells

Abstract

Androgens promote the growth and differentiation of prostate cells through ligand activation of the androgen receptor (AR). Sensitization of the androgenic response by multifunctional growth factor signaling pathways is one of the mechanisms via which AR contributes to the emergence of androgen-independent prostate tumors. The ability of AR to cross-talk with key growth factor signaling events toward the regulation of cell cycle, apoptosis, and differentiation outcomes in prostate cancer cells is established. In this paper, we review the functional interaction between AR and an array of growth factor signal transduction events (including epidermal growth factor; fibroblast growth factor; IGF1; vascular endothelial growth factor; transforming growth factor-beta) in prostate tumors. The significance of this derailed cross-talk between androgens and key signaling networks in prostate cancer progression and its value as a therapeutic forum targeting androgen-independent metastatic prostate cancer is discussed.

Figure 1

Growth factors cross-talk with AR in prostate cancer cells. IGF, FGF, VEGF, and TGFB secreted by the prostate stromal cells activate their receptors and interact with AR signal axis. In prostate epithelial cells, the androgenic signal engages secreted VEGF and TGFB which affects the prostate tumor microenvironment by inducing angiogenesis and stromal cell growth and differentiation. EGF signaling encounters AR signal in a tight control of multiple pathways. Growth factor signaling may proceed via AR signal and regulate the downstream effectors of AR regulating key cellular processes including proliferation, differentiation, apoptosis, and survival of prostate cancer cells.