Hepatocyte Growth Factor and Interleukin-6 in Prostate Cancer Bone Metastasis
Final rept. 15 Feb 2002-14 May 2006
FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
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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. Based on the presence of androgen receptor regulatory elements in the promoter regions of the Interleukin-6 IL-6 and hepatocyte growth factorscatter factor HGFSF genes and the presence of nuclear factor IL-6 binding sites in the promoter of the HGF gene, it is the premise of this project that IL-6 and HGF genes may serve as paradigms of genes that are increased in expression under androgensuppressed conditions. However, initial experiments failed to reveal regulation of HGF and IL-6 by androgen suppression. An analysis of global gene regulation in castrated mice demonstrated that 159 genes were regulated and that Insulin growth Factor Binding Protein-5 demonstrated the most consistent increase in expression. The support provided by the grant fostered the PIs career development to an independent investigator in the field of prostate cancer metastasis to bone. There were several publications supported by the funds from this grant.
- Anatomy and Physiology
- Medicine and Medical Research