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 g ene 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/report er gene constructs has also identified a CRE/ATF motif near the TATA b ox 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 whethe r differences exist in the transcriptional regulation of the TGF-beta 2 gene. We demonstrated that both similarities and differences exist i n the transcriptional regulation of this gene. Common to all cells exa mined to date, the positive regulatory region just upstream of the TAT A box contains an essential CRE/ATF motif that binds at least one tran scription factor, ATF-1, in gel mobility shift assays. However, we did not detect ATF-2 binding to this site with any of the nuclear extract s used. We also determined that the effect of the region between -187 and -78 (relative to the transcription start site) is cell type depend ent. Previous studies have shown that this region acts to reduce the a ctivity of the TGF-beta 2 promoter in differentiated cells derived fro m embryonal carcinoma cells and embryonic stem cells. In direct contra st, this region acts as a strong positive regulatory region in JAR, JE G-3, and MCF-7 cells. The mechanisms responsible for these differing e ffects remain to be established. Interestingly, this region does not a ppear 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 fac tors.