Sp3 is a transcriptional repressor of transforming growth factor-beta receptors.
MCF-7E breast cancer cells express transforming growth factor-beta (TGF-beta) receptors RI and RII in comparison to MCF-7L cells. We present data showing that Sp3 acts as a transcriptional repressor of RI and RII in MCF-7L cells 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 Sp1 oligonucleotide. Southwestern data indicated increased binding of Sp3 to RI and RII promoters in MCF-7L cells, suggesting a correlation between Sp3 binding and reduced expression of TGF-beta receptors 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. Significantly, ectopic Sp3 expression led to repression of RI and RII transcripts in MCF-7E cells. This report demonstrates that inappropriate overexpression of Sp3 is a mechanism that contributes to repression of TGF-beta receptors.
Ammanamanchi
S
S
Department of Surgery, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
Brattain
M G
MG
D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; C497121:SP3 protein, human; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; D004247:DNA