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 TCF-beta type II receptor expression

Transcriptional repression of the TGF-beta type II receptor (RII) is one of the mechanisms leading to TGF-beta resistance. The newly identified epithe lium-specific ets transcription factor ERT/ESX/ELF-3/ESE-1/jen binds to the TGF-beta RII promoter and induces promoter activity. The human gastric can cer cell lines, which show undetectable level of TGF-beta RII mRNA, do not express ERT mRNA, To study the molecular mechanisms of loss of ERT expressi on, we have cloned and characterized the human ERT promoter, DNA transfecti on experiments and electrophoretic mobility shift assays have revealed the existence of a distinct enhancer element (-186 to -177) which we named ESE ((E) under bar RT promoter Specific element). Deletion of the ESE markedly decreased expression of the target gene. ESE interacts with two distinct nu clear 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 e xpressing the ERT mRNA, These results suggest the possibility that inactiva tion of the sequence-specific DNA binding protein to the region from -186 t o -177 contributes to the loss of ERT expression, leading to the loss of TG F-beta type II receptor mRNA in human gastric cancer cell lines.