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Repression of transforming growth factor-β receptor type I promoter expression by Sp1 deficiency

Oncogene volume 19, pages 4660–4667 (2000)Cite this article

Abstract

In this report, we describe the mechanism of TGF-β receptor type I (RI) repression in the GEO human colon carcinoma cells. Treatment of GEO cells with the DNA methyltransferase inhibitor, 5 azacytidine induced RI expression and restored TGF-β response. A stably transfected RI promoter-reporter construct (RI-Luc) expressed higher activity in the 5 aza C treated GEO cells, suggesting the activation of a transactivator for RI transcription. Gel shift analysis indicated enhanced binding of proteins from the 5 aza C treated nuclear extracts to radiolabeled Sp1 oligonucleotides specifically contained in the RI promoter. Protein stability studies after cyclohexamide treatment suggested an increase in the Sp1 protein stability from the 5 aza C treated GEO cells. Further, transfection of Sp1 cDNA into untreated GEO control cells increased RI promoter activity and thus induced RI expression. 5 aza C mediated Sp1 expression in Sp1 deficient GEO colon and MCF-7 breast cancer cells also enhanced the activity of several other Sp1 dependent promoters such as TGF-β receptor type II (RII), Cyclin A and p21/waf1/cip1. These results indicate that restoration of Sp1 in several different types of Sp1 deficient cells leads to enhanced activation of a wide range of Sp1 dependent promoters.

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References

  • Ammanamanchi S, Kim SJ, Sun LZ and Brattain MG. . 1998 J. Biol. Chem. 273: 16527–16534.

  • Attisano L and Wrana JL. . 1998 Curr. Opin. Cell. Biol. 10: 188–194.

  • Birnbaum MJ, van Wijnen AJ, Odgren PR, Last TJ, Suske G, Stein GS and Stein JL. . 1995 Biochemistry 34: 16503–16508.

  • Bloom BB, Humphries DE, Kuang PP, Fine A and Goldstein RH. . 1996 Biochim. Biophys. Acta 1312: 243–248.

  • Brattain MG, Levine AE, Chakrabarty S, Yeoman LC, Willson JK and Long B. . 1984 Cancer Metastasis. Rev. 3: 177–191.

  • Choi S-G, Yi Y, Kim Y-S, Kato M, Chang J, Chung H-W, Hahm K-B, Yang HK, Rhee HH, Bang Y-J and Kim S-J. . 1998 J. Biol. Chem. 273: 110–117.

  • Datto MB, Yu Y and Wang X-F. . 1995 J. Biol. Chem. 270: 28623–28628.

  • Franzen P, ten Dijke P, Ichijo H, Yamashita H, Schulz P, Heldin CH and Miyazono K. . 1993 Cell 75: 681–692.

  • Han I and Kudlow JE. . 1997 Mol. Cell. Biol. 17: 2550–2558.

  • Jackson SP, MacDonald JJ, Lees-Miller S and Tjian R. . 1990 Cell 63: 155–165.

  • Jackson SP and Tjian R. . 1988 Cell 55: 125–133.

  • Jones PA. . 1996 Cancer Res. 56: 2463–2467.

  • Kim DH, Chang JH, Lee KH, Lee HY and Kim SJ. . 1997 J. Biol. Chem. 272: 688–694.

  • Lin HY, Wang XF, Ng-Eaton E, Weinberg RA and Lodish HF. . 1992 Cell 68: 775–785.

  • Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain MG and Willson JKV. . 1995 Science 268: 1336–1338.

  • Massague J. . 1990 Annu. Rev. Cell. Biol. 6: 597–641.

  • Mortensen ER, Marks PA, Shiotani A and Merchant JL. . 1997 J. Biol. Chem. 272: 16540–16547.

  • Myeroff LL, Parsons R, Kim SJ, Hedrick L, Cho KR, Orth K, Mathis M, Kinzler KW, Lutterbaugh J, Park K, Bang YJ, Lee HY, Park J-G, Lynch HT, Roberts AB, Vogelstein B and Markowitz SD. . 1995 Cancer. Res. 55: 5545–5547.

  • Park K, Kim SJ, Bang YJ, Park JG, Kim NK, Roberts AB and Sporn MB. . 1994 Proc. Natl. Acad. Sci. USA. 91: 8772–8776.

  • Periyasamy S, Sun L, Gentry LE and Brattain MG. . 1996 J. Cell. Physiol. 168: 711–720.

  • Pugh BF and Tjian R. . 1990 Cell 61: 1187–1197.

  • Roberts AB and Sporn MB. . 1991 In Peptide Growth Factors and Their Receptors. Springer-Verlag, Heidelberg 419–472.

  • Roos MD, Su K, Baker JR and Kudlow JE. . 1997 Mol. Cell. Biol. 17: 6472–6480.

  • Shen WJ, Kim HS and Tsai SY. . 1995 J. Biol. Chem. 270: 20525–20529.

  • Shin TH, Paterson AJ, Grant JHd, Meluch AA and Kudlow JE. . 1992 Mol. Cell. Biol. 12: 3998–4006.

  • Wang J, Han W, Zborowska E, Liang J, Wang X, Willson JKV, Sun L and Brattain MG. . 1996 J. Biol. Chem. 271: 17366–17371.

  • Wang J, Sun L, Myeroff L, Wang X, Gentry LE, Yang J, Liang J, Zborowska E, Markowitz S, Willson JK and Brattain MG. . 1995 J. Biol. Chem. 270: 22044–22049.

  • Wrana JL, Attisano L, Carcamo J, Zentella A, Doody J, Laiho M, Wang XF and Massague J. . 1992 Cell 71: 1003–1014.

  • Wrana JL, Attisano L, Wieser R, Ventura F and Massague J. . 1994 Nature 370: 341–347.

  • Yingling JM, Wang XF and Bassing CH. . 1995 Biochim. Biophys. Acta 1242: 115–136.

  • Yoshizumi M, Wang H, Hseih C-H, Sibinga NES, Parrella MA and Lee M-E. . 1997 J. Biol. Chem. 272: 22259–22264.

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Acknowledgements

This work was supported by National Institutes of Health grants CA 38173 and CA 72001. We thank R Goldstein for kindly providing the RI-Luc construct used in this study.

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Author notes

  1. Sumudra Periyasamy and Sudhakar Ammanamanchi: S Periyasamy and S Ammanamanchi contributed equally to this work

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo, 43614, Ohio, OH, USA

    Sumudra Periyasamy & Manoranjani PM Tillekeratne

  2. Department of Surgery, The University of Texas Health Science Center, San Antonio, 78229, Texas, TX, USA

    Sudhakar Ammanamanchi & Michael G Brattain

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  1. Sumudra Periyasamy
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Periyasamy, S., Ammanamanchi, S., Tillekeratne, M. et al. Repression of transforming growth factor-β receptor type I promoter expression by Sp1 deficiency. Oncogene 19, 4660–4667 (2000). https://doi.org/10.1038/sj.onc.1203822

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