Sp3 is a transcriptional repressor of transforming growth factor-beta receptors

MCF-7E breast cancer cells express transforming growth factor-beta (TGF-bet a) receptors RI and RII in comparison to MCF-7L cells. We present data show ing that Sp3 acts as a transcriptional repressor of RI and RII in MCF-7L ce lls and GEO colon cancer cells. MCF-7L and GEO cells express high levels of Sp3 protein. Gel shift analysis indicated enhanced binding of Sp3 from MCF -7L cells to a consensus Spl oligonucleotide. Southwestern data indicated i ncreased binding of Sp3 to RI and RII promoters in MCF-7L cells, suggesting a correlation between Sp3 binding and reduced expression of TGF-P receptor s in MCF-7L cells. Cotransfection of CMV-Sp3 cDNA with RI and RII promoter- luciferase reporter constructs decreased RI and RII promoter activities by 70% in MCF-7E and GEO cells. Southwestern analysis detected the binding of transiently expressed Sp3 to RI and RII promoters in MCF-7E cells. Signific antly, ectopic Sp3 expression led to repression of RI and RII transcripts i n MCF-7E cells. This report demonstrates that inappropriate overexpression of Sp3 is a mechanism that contributes to repression of TGF-beta receptors.