The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenes
Technical Report,30 Sep 2011,29 Sep 2015
Thomas Jefferson University Philadelphia United States
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These studies were conducted to determine the function of DACH1 in regulating prostate cancer growth in vitro and in vivo, and to determine the normal function of DACH1 in prostate development. We demonstrated that DACH1 suppresses prostate cancer cellular growth induced by ErbB2. We demonstrated similar mechanisms govern DACH1 restrain of prostate tumorigenesis promoted by Ras, c-Myc and c-Src. We identified the key molecular targets regulated by DACH1 in vitro and in vivo and showed using ChIP analysis the binding of DACH1 tokey target genes. We used genetic deletion studies to identify the key function for DACH1 in restraining cytokine secretion. IL-8 and IL-6 are the key cytokines demonstrated to promote prostate cancer growth andwe showed that DACH1 is the key endogenous mechanism governing restraint of prostate epithelial cell cytokinesecretion IL-8 and IL-6.