TGFBR3 loss and consequences in prostate cancer

BACKGROUND. Resistance to transforming growth factor-beta (TGF-β) is important in tumorigenesis. TGF-β resistance mechanisms in prostate cancer are not well understood. METHODS. We have conducted a systematic analysis of TGF-β pathway components with a meta-analysis of seven microarray studies using Oncomine and evaluated the results of TGFBR3 expression in prostate cell lines. Furthermore, we knocked down TGFBR3 in prostate epithelial cells and analyzed the consequences of TGFBR3 knockdown. RESULTS. We found that TGFBR3 is the TGF-β component most commonly downregulated among localized human prostate cancer studies. TGFBR3 knockdown led to focus formation and enhanced expression of CD133, a marker found on prostate cancer stem cells. DNA microarray analysis of TGFBR3 knockdown cells identified 101 genes regulated by TGFBR3. Seven of these genes show a corresponding decrease in clinical prostate cancer specimens, which include genes involved in prostate mass and vasculature. CONCLUSIONS. TGFBR3 downregulation is an important step in prostate tumorigenesis.