TGF-Beta Antibody for Prostate Cancer: Role of ERK

摘要: Abstract : Characteristics of aggressive prostate cancers (CaP) include a loss sensitivity to physiologic levels TGF- due in part receptors (T Rs) methylation mediated by DNA methyltransferase (DNMT). However, the mechanisms underlying these alterations remain undetermined. We used human CaP cell lines with varying degrees invasive capability, and samples elucidate mechanism(s) associated insensitivity disease outcome following radical prostatectomy. determined that more cells had significantly higher increased expression DNMTs compared benign less cancer cells. In contrast, T Rs was reduced Blockade signaling or extracellular signal-regulated kinases (ERK) dramatic decrease DNMTs, coincident increase addition, there time dependent positive correlation between treatment p-ERK demonstrated negative expression. Inhibition an vivo xenograft model using 1D11 inhibition tumor growth but also downregulation DNMTs. Finally, independent Gleason grade, induced DNMT1 biochemical recurrence Our findings derived may induce which subsequently results hypermethylation its own inhibition. ERK activation mediates this feedback loop is potential CaP. pathway have future clinical implications as therapeutic target prognostic tool.