Sequence-specific enhancer binding protein is responsible for the differential expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines: Implication for the loss of TGF-β type II receptor expression

Transcriptional repression of the TGF-β type II receptor (RII) is one of the mechanisms leading to TGF-β resistance. The newly identified epithelium-specific ets transcription factor ERT/ESX/ELF-3/ESE-1/jen binds to the TGF-β RII promoter and induces promoter activity. The human gastric cancer cell lines, which show undetectable level of TGF-β RII mRNA, do not express ERT mRNA. To study the molecular mechanisms of loss of ERT expression, we have cloned and characterized the human ERT promoter. DNA transfection experiments and electrophoretic mobility shift assays have revealed the existence of a distinct enhancer element (-186 to -177) which we named ESE (ERT promoter specific element). Deletion of the ESE markedly decreased expression of the target gene. ESE interacts with two distinct nuclear protein complexes, at least one of which appears to be inactivated in a cell line which does not express the ERT mRNA, compared to a cell line expressing the ERT mRNA. These results suggest the possibility that inactivation of the sequence-specific DNA binding protein to the region from -186 to -177 contributes to the loss of ERT expression, leading to the loss of TGF-β type II receptor mRNA in human gastric cancer cell lines.