Abstract 3184: TGF-β1 signaling inhibits proliferation but promotes motility with progression to castrate-resistant prostate cancer

Transforming growth factor-beta1 (TGF-B1) is a tumor suppressor in normal and early stage prostate cancer (PCa) cells, but exerts pro-tumorigenic effects during progression to metastatic disease, and correlates with poor prognosis. However, the mechanisms whereby TGF-B1 induces pro-metastatic action are uknown. Previously it was reported that the LNCaP cell line was insensitive to TGF-B-mediated growth suppression. Thus we sought to examine the TGF-B1-induced proliferative response of increasingly metastatic, lineage-related LNCaP sublines.Under reduced serum conditions we show that TGF-B1 inhibits cell proliferation profoundly and promotes apoptosis in castrate-insensitive LNCaP sublines, whereas inhibition of cell proliferation is marginal in LNCaP cells. Growth inhibitory effects and apoptosis are mediated by active TGF-B receptors, TBRII and TBRI, and the downstream Smad2/3 effectors. Knock down of TBRII with a dominant negative construct, as well as inhibition of kinase activity abrogrates these effects. Additionally, we show that TGF-B enhances cytoskeletal rearrangements and increases motility on selected extracellular matrices in metastatic LNCaP sublines.TGF-B signaling in castrate-resistant PCa cell lines is more robust than in hormonally sensitive clones and leads to selective activation of cell motilty that influences PCa cell metastatic behavior with potential consequences for bone colonization.Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3184.