We also established that TIMP-1 enhances whereas knockdown of TIMP-1 inhibits prostate CAF proliferation and migration and that TIMP-1 promotes activation of ERK1/2 kinase in these CAFs (Figures 6-7 and Figure 8B) but not in prostate cancer cells (Figure 8C) in vitro, suggesting that the pro-tumor effect of TIMP-1 is indirectly exerted through the cancer associated fibroblasts, which in turn provides a pro-tumor microenvironment to facilitate the cancer progression (Figure 9). This evidence concerns the gene TIMP1 and Familial prostate cancer.