Skip to main content

Advertisement

SpringerLink
Log in

Transcription factor AP1 binds the functional region of the promoter and regulates gene expression of human PPARdelta in LoVo cell

  • Research Article
  • Published:
Tumor Biology

Abstract

Peroxisome proliferator-activated receptor δ gene (PPARδ) is correlated with carcinogenesis of colorectal cancer, but the regulation of its gene transcription remains unclear. We herein report that AP1 binds the promoter and regulates PPARδ gene expression. With a luciferase reporter system, we identified a functional promoter region of 30 bp of PPARδ gene by deletion and electrophoretic mobility shift assays (EMSA). Using site-directed mutagenesis and decoy analyses, we demonstrated that AP1 bound the functional transcriptional factor binding site in a region extending from −176 to −73 of the PPARδ promoter, which was confirmed using EMSA and supershift assays. Consequently, inhibition of the AP1 binding site led to decreased PPARδ mRNA. Our study demonstrated that AP1 is the transcriptional factor that contributes to PPARδ expression in LoVo cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Michalik L, Wahli W. Involvement of PPAR nuclear receptors in tissue injury and wound repair. J Clin Invest. 2006;116:598–606.

    Article  PubMed  CAS  Google Scholar 

  2. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20:649–88.

    Article  PubMed  CAS  Google Scholar 

  3. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta. 1996;1302:93–109.

    Article  PubMed  CAS  Google Scholar 

  4. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43:527–50.

    Article  PubMed  CAS  Google Scholar 

  5. Hansen MK, Connolly TM. Nuclear receptors as drug targets in obesity, dyslipidemia and atherosclerosis. Curr Opin Investig Drugs. 2008;9:247–55.

    PubMed  CAS  Google Scholar 

  6. Torra IP, Chinetti G, Duval C, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice. Curr Opin Lipidol. 2001;12:245–54.

    Article  PubMed  CAS  Google Scholar 

  7. Wang N. PPAR-delta in vascular pathophysiology. PPAR Res. 2008;2008:164163.

    PubMed  Google Scholar 

  8. Meissner M, Hrgovic I, Doll M, Kaufmann R. PPARδ agonists suppress angiogenesis in a VEGFR2-dependent manner. Arch Dermatol Res. 2011;303:41–7.

    Article  PubMed  CAS  Google Scholar 

  9. Kostadinova R, Montagner A, Gouranton E, Fleury S, Guillou H, et al. GW501516-activated PPARβ/δ promotes liver fibrosis via p38-JNK MAPK-induced hepatic stellate cell proliferation. Cell Biosci. 2012;2:34.

    Article  PubMed  CAS  Google Scholar 

  10. Kliewer SA, Lehmann JM, Milburn MV, Willson TM. The PPARs and PXRs: nuclear xenobiotic receptors that define novel hormone signaling pathways. Recent Prog Horm Res. 2000;54:345–67.

    Google Scholar 

  11. Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998;47:507–14.

    Article  PubMed  CAS  Google Scholar 

  12. He TC, Chan TA, Vogelstein B, Kinzler KW. PPARd is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999;99:335–45.

    Article  PubMed  CAS  Google Scholar 

  13. Takayama O, Yamamoto H, Damdinsuren B, Sugita Y, Ngan CY, et al. Expression of PPARd in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology. Br J Cancer. 2006;95:889–95.

    Article  PubMed  CAS  Google Scholar 

  14. Harman FS, Nicol CJ, Marin HE, Ward JM, Gonzalez FJ, et al. Peroxisome proliferator-activated receptor-d attenuates colon carcinogenesis. Nat Med. 2004;10:481–3.

    Article  PubMed  CAS  Google Scholar 

  15. Reed KR, Sansom OJ, Hayes AJ, Gescher AJ, Winton DJ, et al. PPAR delta status and Apc-mediated tumorigenesis in the mouse intestine. Oncogene. 2004;23:8992–6.

    Article  PubMed  CAS  Google Scholar 

  16. Park BH, Vogelstein B, Kinzler KW. Genetic disruption of PPARd decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci USA. 2001;98:2598–603.

    Article  PubMed  CAS  Google Scholar 

  17. Gupta RA, Wang D, Katkuri S, Wang H, Dey SK, et al. Activation of nuclear hormone receptor peroxisome proliferator activated recaptured accelerates intestinal adenoma growth. Nat Med. 2004;10:245–7.

    Article  PubMed  CAS  Google Scholar 

  18. Zuo X, Peng Z, Moussalli MJ, Morris JS, Broaddus RR, et al. Targeted genetic disruption of peroxisome proliferator-activated receptor-delta and colonic tumorigenesis. J Natl Cancer Inst. 2009;101:762–7.

    Article  PubMed  CAS  Google Scholar 

  19. Gupta RA, Tan J, Krause WF, Geraci MW, Willson TM, et al. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor δ in colorectal cancer. Proc Natl Acad Sci USA. 2000;97:13275–80.

    Article  PubMed  CAS  Google Scholar 

  20. Shao J, Sheng H, DuBois RN. Peroxisome proliferator-activated receptors modulate K-Ras-mediated transformation of intestinal epithelial cells. Cancer Res. 2002;62:3282–8.

    PubMed  CAS  Google Scholar 

  21. Di-Poï N, Tan NS, Michalik L, Wahli W, Desvergne B. Antiapoptotic role of PPARβ in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol Cell. 2002;10:721–33.

    Article  PubMed  Google Scholar 

  22. Wang D, Wang H, Guo Y, Ning W, Katkuri S, et al. Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancer progression. Proc Natl Acad Sci U S A. 2006;103:19069–74.

    Article  PubMed  CAS  Google Scholar 

  23. Kwak H, Hwang I, Kim JH, Kim MY, Yang JS, et al. Modulation of transcription by the peroxisome proliferator-activated receptor δ-binding RNA aptamer in colon cancer cells. Mol Cancer Ther. 2009;8:2664–73.

    Article  PubMed  CAS  Google Scholar 

  24. Yang L, Olsson B, Pfeifer D, Jönsson JI, Zhou ZG, et al. Knockdown of peroxisome proliferator-activated receptor-β induces less differentiation and enhances cell-fibronectin adhesion of colon cancer cells. Oncogene. 2010;29:516–26.

    Article  PubMed  CAS  Google Scholar 

  25. Malnou CE, Brockly F, Favard C, Moquet-Torcy G, Piechaczyk M, et al. Heterodimerization with different Jun proteins controls c-Fos intranuclear dynamics and distribution. J Biol Chem. 2010;285:6552–62.

    Article  PubMed  CAS  Google Scholar 

  26. Chen W, Bowden GT. Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes. Oncogene. 1999;18:7469–76.

    Article  PubMed  CAS  Google Scholar 

  27. Jochum W, Passegue E, Wagner EF. AP-1 in mouse development and tumorigenesis. Oncogene. 2001;20:2401–12.

    Article  PubMed  CAS  Google Scholar 

  28. Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 2003;39:615–47.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Genetics and Molecular Biology, Xi’an Jiaotong University College of Medicine, Xi’an, 710061, Shaanxi, People’s Republic of China

    Xiaogang Jiang, Xudong Yang, Yan Han & Shemin Lu

Authors
  1. Xiaogang Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xudong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shemin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shemin Lu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, X., Yang, X., Han, Y. et al. Transcription factor AP1 binds the functional region of the promoter and regulates gene expression of human PPARdelta in LoVo cell. Tumor Biol. 34, 3619–3625 (2013). https://doi.org/10.1007/s13277-013-0943-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-0943-4

Keywords

Search

Navigation