Attenuated Transforming Growth Factor Beta Signaling as a Therapeutic for Prostate Cancer Progression; Annual rept. 1 Feb 2007-31 Jul 2008

摘要

The purpose or this proposal is to determine the effects of stromal TGF-beta signaling inhibition by SD-208 (a TbetaRI-specific inhibitor) on prostate cancer growth, by using both in vitro prostate cancer/stromal cell co- culture model and in vivo xenograft model. In this initial funding year, we have tested the SD-208 efficiency in inhibiting TGF-beta signaling in prostate stromal cells. We further demonstrated that TOF-beta signaling in prostate stromal cells induced a complex response in prostate cancer cells. This response can be inhibited by either knockout of TbetaRII from mouse prostate stromal cells or by addition for SD-208 into the co-culture for human prostate cancer cells and human prostate stromal cells. We are using cDNA microarray and qPCR to identify the potential signaling molecules regulating these events. Based on these in vitro results, we are now carrying out the in vivo studies. We expect to finish all these studies at the conclusion for this award and present these sets for data in the final report.