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The hypothesis of this grant proposal is that androgen-ablative therapy paradoxically increases growth factor secretion from bone stromal cells and that this may stimulate the growth of prostate cancer metastases. We proposed to test this hypothesis using IL-6 and HGF/SF as paradigms of androgen regulated growth stimulators. However, two separate experimental approaches did not demonstrate an increase in IL-6 or HGF/SF gene expression in androgen- deprived mouse bone. As a result of this initial negative investigation in task 1 we decided to take a broad approach to identify genes up-regulated by androgen deprivation in mouse bone. This approach has revealed multiple genes overexpressed upon androgen-ablation that may regulate growth factor systems involved in the crosstalk between the bone environment and prostate cancer cells.