Skip to main content
Top
Published in: Tumor Biology 6/2013

01-12-2013 | Research Article

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

Authors: Xiaogang Jiang, Xudong Yang, Yan Han, Shemin Lu

Published in: Tumor Biology | Issue 6/2013

Login to get access

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.
Literature
1.
go back to reference Michalik L, Wahli W. Involvement of PPAR nuclear receptors in tissue injury and wound repair. J Clin Invest. 2006;116:598–606.PubMedCrossRef Michalik L, Wahli W. Involvement of PPAR nuclear receptors in tissue injury and wound repair. J Clin Invest. 2006;116:598–606.PubMedCrossRef
2.
go back to reference Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20:649–88.PubMedCrossRef Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20:649–88.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43:527–50.PubMedCrossRef Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43:527–50.PubMedCrossRef
5.
go back to reference Hansen MK, Connolly TM. Nuclear receptors as drug targets in obesity, dyslipidemia and atherosclerosis. Curr Opin Investig Drugs. 2008;9:247–55.PubMed Hansen MK, Connolly TM. Nuclear receptors as drug targets in obesity, dyslipidemia and atherosclerosis. Curr Opin Investig Drugs. 2008;9:247–55.PubMed
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference Wang N. PPAR-delta in vascular pathophysiology. PPAR Res. 2008;2008:164163.PubMed Wang N. PPAR-delta in vascular pathophysiology. PPAR Res. 2008;2008:164163.PubMed
8.
go back to reference Meissner M, Hrgovic I, Doll M, Kaufmann R. PPARδ agonists suppress angiogenesis in a VEGFR2-dependent manner. Arch Dermatol Res. 2011;303:41–7.PubMedCrossRef Meissner M, Hrgovic I, Doll M, Kaufmann R. PPARδ agonists suppress angiogenesis in a VEGFR2-dependent manner. Arch Dermatol Res. 2011;303:41–7.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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. 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.
11.
go back to reference Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998;47:507–14.PubMedCrossRef Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998;47:507–14.PubMedCrossRef
12.
go back to reference He TC, Chan TA, Vogelstein B, Kinzler KW. PPARd is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999;99:335–45.PubMedCrossRef He TC, Chan TA, Vogelstein B, Kinzler KW. PPARd is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999;99:335–45.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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 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
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference Jochum W, Passegue E, Wagner EF. AP-1 in mouse development and tumorigenesis. Oncogene. 2001;20:2401–12.PubMedCrossRef Jochum W, Passegue E, Wagner EF. AP-1 in mouse development and tumorigenesis. Oncogene. 2001;20:2401–12.PubMedCrossRef
28.
go back to reference Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 2003;39:615–47.PubMedCrossRef Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 2003;39:615–47.PubMedCrossRef
Metadata
Title
Transcription factor AP1 binds the functional region of the promoter and regulates gene expression of human PPARdelta in LoVo cell
Authors
Xiaogang Jiang
Xudong Yang
Yan Han
Shemin Lu
Publication date
01-12-2013
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2013
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-0943-4

Other articles of this Issue 6/2013

Tumor Biology 6/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine