Transcriptional regulation of the TGF-beta 2 gene in choriocarcinoma cells and breast carcinoma cells: differential utilization of Cis-regulatory elements.

Previous studies have shown that the transcription of the TGF-beta 2 gene is controlled by at least one negative and two positive regulatory regions in differentiated cells derived from both embryonal carcinoma cells and embryonic stem cells. The use of TGF-beta 2 promoter/reporter gene constructs has also identified a CRE/ATF motif near the TATA box that appears to heavily influence the transcription of the TGF-beta 2 gene. In this study, two choriocarcinoma cell lines, JAR and JEG-3, and the breast cancer cell line, MCF-7, were used to determine whether differences exist in the transcriptional regulation of the TGF-beta 2 gene. We demonstrated that both similarities and differences exist in the transcriptional regulation of this gene. Common to all cells examined to date, the positive regulatory region just upstream of the TATA box contains an essential CRE/ATF motif that binds at least one transcription factor, ATF-1, in gel mobility shift assays. However, we did not detect ATF-2 binding to this site with any of the nuclear extracts used. We also determined that the effect of the region between -187 and -78 (relative to the transcription start site) is cell type dependent. Previous studies have shown that this region acts to reduce the activity of the TGF-beta 2 promoter in differentiated cells derived from embryonal carcinoma cells and embryonic stem cells. In direct contrast, this region acts as a strong positive regulatory region in JAR, JEC-3, and MCF-7 cells. The mechanisms responsible for these differing effects remain to be established. Interestingly, this region does not appear to contain sequence motifs that bind known transcription factors. Thus, this region is likely to bind one or more novel transcription factors or contain novel recognition sites for known transcription factors.