Tristetraprolin regulates prostate cancer cell growth through suppression of E2F1.

Tristetraprolin regulates prostate cancer cell growth through suppression of E2F1.
J Microbiol Biotechnol. 2013 Oct 22;
Authors: Lee HH, Lee SR, Leem SH
Abstract
The transcription factor E2F1 is active during the G1 to S transition and is involved in cell cycle and progression. A recent study reported that increased E2F1 is associated with DNA damage and tumour development in several tissues using transgenic models. Here, we show that E2F1 expression is regulated by tristetraprolin (TTP) in prostate cancer. Overexpression of TTP decreased the stability of E2F1 mRNA and the expression level of E2F1. In contrast, inhibition of TTP using siRNA increased the E2F1 expression. E2F1 mRNA contains three AREs within the 3'UTR and TTP destabilized a luciferase mRNA that contained the E2F1 mRNA 3'UTR. Analyses of point mutants of the E2F1 mRNA 3'UTR demonstrated that ARE2 was mostly responsible for the TTP-mediated destabilization of E2F1 mRNA. RNA EMSA revealed that TTP binds directly to the E2F1 mRNA 3'UTR of ARE2. Moreover, treatment with siRNA against TTP increased the proliferation of PC3 human prostate cancer cells. Taken together, these results demonstrate that E2F1 mRNA is a physiological target of TTP and suggests that TTP controls proliferation as well as migration and invasion through regulation of E2F1 mRNA stability.
PMID: 24150491 [PubMed - as supplied by publisher]

Source: Journal of Microbiology and Biotechnology - October 22, 2013 Category: Biotechnology Authors: Lee HH, Lee SR, Leem SH Tags: J Microbiol Biotechnol Source Type: research