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Peroxisome-proliferator-activated receptors γ and β/δ mediate vascular endothelial growth factor production in colorectal tumor cells

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Abstract

Background

Peroxisome-proliferator-activated receptors (PPARs) are nuclear receptors for fatty acids and their derivatives. PPAR subtypes PPARγ and PPARβ/δ are suspected to modulate cancer development in the colon, but their exact role is still discussed controversially.

Methods

The present study investigated the impact of PPARγ and PPARβ/δ on vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX-2) expressions induced by synthetic and physiological agonists in the colorectal tumor cell lines SW480 and HT29 using reporter gene assays, qRT-PCR and ELISA.

Results

Activation of both PPARγ and PPARβ/δ induced expression of VEGF mRNA and protein in a PPAR-dependent way. The PPARγ agonists ciglitazone and PGJ2 were the most effective inducers with up to ninefold and threefold increases in VEGF mRNA in SW480 and HT29 cultures, respectively. VEGF secretion was doubled in both cell lines. The PPARβ/δ agonists GW501516 and PGI2 caused stimulations of only 1.5-fold in both cell lines. In addition, all PPAR agonists induced COX-2 mRNA and secretion of the COX-2 product PGE2 in HT29 cells. However, this effect was not blocked by knock-down of PPAR expression nor was it essential for VEGF expression as shown by the lack of effect of the COX-2 inhibitor SC236.

Conclusion

In summary, our results identify both PPARγ and PPARβ/δ as an alternative COX-independent mechanism of VEGF induction in colorectal tumor cells.

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Abbreviations

COX:

Cyclooxygenase

PG:

Prostaglandin

PPAR:

Peroxisome-proliferator-activated receptor

PPRE:

Peroxisome-proliferator response element

K20:

Cytokeratin 20

ANGPTL4:

Angiopoietin-like 4

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Acknowledgments

This study was supported by grants from the Austrian National Bank (#10630) and from the Herzfelder’sche Familienstiftung.

Conflict of interest statement

We have no conflict of interest to declare.

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Author notes

  1. Clemens Röhrl

    Present address: Division for Pathobiochemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria

Authors and Affiliations

  1. Department of Medicine 1, Clinic for Internal Medicine I, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria

    Clemens Röhrl, Ulrike Kaindl, Inga Koneczny, Xenia Hudec, David M. Baron & Brigitte Marian

  2. Department for Nutritional Sciences, University of Vienna, Vienna, Austria

    Jürgen S. König

  3. Children’s Cancer Research Institute (CCRI), Vienna, Austria

    Ulrike Kaindl

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  1. Clemens Röhrl
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Corresponding author

Correspondence to Brigitte Marian.

Additional information

C. Röhrl, U. Kaindl authors contributed equally to this work.

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Röhrl, C., Kaindl, U., Koneczny, I. et al. Peroxisome-proliferator-activated receptors γ and β/δ mediate vascular endothelial growth factor production in colorectal tumor cells. J Cancer Res Clin Oncol 137, 29–39 (2011). https://doi.org/10.1007/s00432-010-0856-1

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  • DOI: https://doi.org/10.1007/s00432-010-0856-1

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