Ets1 and heat shock factor 1 regulate transcription of the Transformer 2[beta] gene in human colon cancer cells

Background Transformer (Tra) 2[beta] is a member of the serine/arginine-rich (SR)-like protein family that regulates alternative splicing of numerous genes in a concentration-dependent manner. Several types of cancer cells up-regulate Tra2[beta] expression, while the regulatory mechanism of Tra2[beta] expression remains to be elucidated. In this study, we examined the transcriptional regulation and possible functions of Tra2[beta] in human colon cancer cells. Methods We cloned 959 bp-upstream of the human TRA2[beta] 5'-flank into luciferase constructs. Chromatin immunoprecipitation (ChIP) was employed to identify crucial cis element(s) and trans activator(s) of the TRA2[beta] promoter. Tra2[beta] expression in the human colon and colon cancer tissues was examined by immunohistochemistry. Results In response to sodium arsenite, colon cancer cells (HCT116) increased levels of TRA2[beta]1 mRNA encoding a functional, full-length Tra2[beta] with a peak around 6 h without changing its mRNA stability. Transient expression assays using a reporter gene driven by serially truncated TRA2[beta] promoters and Chip assay demonstrated that an Ets1-binding site present at -64 to -55 bp was crucial for basal transcription, while three heat shock elements (HSEs) located at -145 to -99 bp mediated the oxidant-induced transactivation of TRA2[beta]. Tra2[beta] knockdown caused apoptosis of HCT116 cells. Tra2[beta] were preferentially expressed in proliferative compartment of normal human colonic glands and adenocarcinomas, where Ets1 and heat shock factor 1 were also highly expressed. Conclusions Our results suggest that oxidative stress-responsive Tra2[beta] may play an important role in colon cancer growth.