Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Vitamin D3 receptor/Sp1 complex is required for the induction of p27Kip1 expression by vitamin D3

Abstract

1α,25-dihydroxyvitamin D3 (vitamin D3) has been shown to upregulate p27Kip1 expression via Sp1 and NF-Y binding sites in the p27Kip1 promoter. However, whether vitamin D3 receptor (VDR) involves in this process is unclear. In this study, we demonstrated that expression of VDR in SW620 cells, which exhibited low level of endogenous VDR, increased vitamin D3-stimulated p27Kip1 promoter activity. On the contrary, suppression of Sp1 expression by small interference RNA reduced the stimulation of p27Kip1 promoter activity by vitamin D3 in LNCaP cells. DNA affinity precipitation assay and chromatin immunoprecipitation assay showed that VDR bound to the p27Kip1 promoter in vitro and in vivo. In addition, we also demonstrated that VDR interacted with Sp1 in vitro and in cells. Collectively, our results suggest that VDR is involved in the induction of p27Kip1 by vitamin D3 and may interact with Sp1 to modulate the expression of target genes that lack VDR response element (VDRE) in their promoters.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Boyan BD, Sylvia VL, Dean DD and Schwartz Z . (2002). Steroids, 67, 421–427.

  • Buitrago C, Vazquez G, De Boland AR and Boland RL . (2000). J. Cell. Biochem., 79, 274–281.

  • Christakos S, Barletta F, Huening M, Dhawan P, Liu Y, Porta A and Peng X . (2003). J. Cell. Biochem., 88, 238–244.

  • Deluca HF and Cantorna MT . (2001). FASEB J., 15, 2579–2585.

  • Dong L, Wang W, Wang F, Stoner M, Reed JC, Harigai M, Kladde M, Vyhlidal C and Safe S . (1999). J. Biol. Chem., 274, 32099–32107.

  • Duan R, Porter W and Safe S . (1998). Endocrinology, 139, 1981–1990.

  • Gareth IO, Jennifer KR, Lin T, Glenn T and Kathryn B . (1998). J. Biol. Chem., 273, 10696–10701.

  • Ge Y, Jensen TL, Matherly LH and Taub JW . (2002). Biochem. Biophys. Acta, 1579, 73–80.

  • Gurlek A, Pittelkow MR and Kumar R . (2002). Endocr. Rev., 23, 763–786.

  • Guyton KZ, Kensler TW and Posner GH . (2001). Annu. Rev. Pharmacol. Toxicol., 41, 421–442.

  • Harper JW . (1997). Cancer Surv., 29, 91–107.

  • Hengst L and Reed SI . (1998). Curr. Top. Microbiol. Immunol., 227, 25–41.

  • Hewetson A and Chilton BS . (2003). J. Biol. Chem., 278, 40177–40185.

  • Huang YC, Chuang LY and Hung WC . (2002). Mol. Pharmacol., 62, 1515–1521.

  • Inoue T, Kamiyama J and Sakai T . (1999). J. Biol. Chem., 274, 32309–32317.

  • Johnson CS, Hershberger PA and Trump DL . (2002). Cancer Metastas. Rev., 21, 147–158.

  • Jones G, Strugnell SA and DeLuca HF . (1998). Physiol. Rev., 78, 1193–1231.

  • Khorasanizadeh S and Rastinejad F . (2001). Trends Biochem. Sci., 26, 384–390.

  • Kim K, Thu N, Saville B and Safe S . (2003). Mol. Endocrinol., 17, 804–817.

  • Kumagai T, O’Kelly J, Said JW and Koeffler HP . (2003). J. Natl. Cancer Inst., 95, 896–905.

  • Liu LT, Chang HC, Chiang LC and Hung WC . (2003). Cancer Res., 63, 3069–3072.

  • Liu W, Asa SL, Fantus IG, Walfish PG and Ezzat S . (2002). Am. J. Pathol., 160, 511–519.

  • Liu X, Lee MT, Cohen M, Bommakanti M and Freedman LP . (1996). Genes Dev., 10, 142–153.

  • Lok CN, Lang AJ, Mirski SE and Cole SP . (2002). Biochem. J., 368, 741–751.

  • Martinez ME, Giovannucci EL, Colditz GA, Stampfer MJ, Hunter DJ, Speizer FE, Wing A and Willett WC . (1996). J. Natl. Cancer Inst., 88, 1375–1382.

  • Minami S, Ohtani-Fujita N, Igata E, Tamaki T and Sakai T . (1997). FEBS Lett., 411, 1–6.

  • Narvaez CJ, Zinser G and Welsh J . (2001). Steroids, 66, 301–308.

  • Olefsky JM . (2001). J. Biol. Chem., 276, 36863–36864.

  • Palmer HG, Gonzalez-Sancho JM, Espada J, Berciano MT, Puig I, Baulida J, Quintanilla M, Cano A, de Herreros AG, Lafarga M and Munoz A . (2001). J. Cell. Biol., 154, 369–387.

  • Pan MR and Hung WC . (2002). J. Biol. Chem., 277, 32775–32780.

  • Rotheneder H, Geymayer S and Haidweger E . (1999). J. Mol. Biol., 306, 201–212.

  • Safe S . (2001). Vitam. Horm., 62, 231–252.

  • Schwartz Z, Shaked D, Hardin RR, Gruwell S, Dean DD, Sylvia VL and Boyan BD . (2003). Steroids, 66, 423–437.

  • Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ and Evans SR . (1993). Cancer Res., 53, 3712–3718.

  • Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ, Uskokovic MR, Brenner RV and Evans SR . (1994). Cancer Res., 54, 4057–4064.

  • Shigeaki K . (2000). J. Biochem., 127, 717–722.

  • Sun G, Porter W and Safe S . (1998). Mol. Endocrinol., 12, 882–890.

  • Towers TL, Luisi BF, Asianov A and Freedman LP . (1993). Proc. Natl. Acad. Sci. USA, 90, 6310–6314.

  • Valor LM, Campos-Caro A, Carrasoo-Serrano C, Ortiz JA, Ballesta JJ and Criado M . (2002). J. Biol. Chem., 277, 8866–8876.

  • Vidal M, Ramana CV and Dusso AS . (2002). Mol. Cell. Biol., 22, 2777–2787.

  • Wang F, Hoivik D, Pollenz R and Safe S . (1998). Nucliec Acids Res., 26, 3044–3052.

  • Wang W, Dong L, Saville B and Safe S . (1999). Mol. Endocrinol., 13, 1373–1387.

  • Yang ES, Maiorino CA, Roos BA, Knight SR and Burnstein KL . (2002). Mol. Cell. Endocrinol., 186, 69–79.

  • Zhang DE, Hetherington CJ, Gonzalez DA, Chen HM and Tenen DG . (1994). J. Immunol., 153, 3276–3284.

  • Zhu Y, Saunders MA, Yeh H, Deng WG and Wu KK . (2002). J. Biol. Chem., 277, 6923–6928.

Download references

Acknowledgements

We thank Dr H Rotheneder, Dr LP Freedman and Dr T Sakai for providing experimental materials. This study was supported by MOE Program for Promoting Academic Excellent of Universities under the grant number 91-B-FA09-1-4 to Wen-Chun Hung.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wen-Chun Hung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, YC., Chen, JY. & Hung, WC. Vitamin D3 receptor/Sp1 complex is required for the induction of p27Kip1 expression by vitamin D3. Oncogene 23, 4856–4861 (2004). https://doi.org/10.1038/sj.onc.1207621

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207621

Keywords

This article is cited by

Search

Quick links