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PPARβ/δ Agonist Increases the Expression of PGE2 Receptor Subtype EP4 in Human Lung Carcinoma Cells

  • Jeffrey D. Ritzenthaler
  • Jesse Roman
  • ShouWei Han
Part of the Methods in Molecular Biology™ book series (MIMB, volume 512)

Summary

Lung carcinoma remains one of the most common malignant tumors in the world despite recent advancements in the development of new chemotherapeutic agents for its treatment. Therefore, novel approaches for drug target discovery play an important role in the effort to help extend its dismal 5-year survival rate (<15%). Many mechanisms contribute to oncogenic transformation in carcinoma cells in the lung and recent evidence indicates that the overproduction of prostaglandin E2 (PGE2), and the prostag-landin E2 receptor subtype, EP4, promote the growth and progression of human nonsmall cell lung carcinoma (NSCLC), the most common lung carcinoma. Peroxisome proliferator-activated receptor beta/ delta (PPARβ/δ), one of the nuclear hormone ligand-dependent transcription factors, has recently been reported to be involved in tumorigeniCity. We have shown that NSCLC cells express PPARβ/δ protein and that treatment with a selective PPARβ/δ agonist, GW501516, stimulated the expression of EP4 and induced NSCLC cell proliferation. In addition, this PPARβ/δ agonist also induced EP4 promoter activity through the binding of C/EBP to the NF-IL6 site in the EP4 promoter. Therefore, PPARβ/δ activation represents a novel molecular mechanism for regulating human cancer cell growth.

Key words

PPARβ/δ EP4 NSCLC Transfection EMSA 

Notes

Acknowledgments

We would like to thank Dr. William L. Smith (University of Michigan) for providing the mouse EP4 constructs. This work was supported by American Lung Association Grant RG-10215N (S.W.H.) and by a Merit Review Grant from the Department of Veterans Affairs (J.R.).

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jeffrey D. Ritzenthaler
    • 1
  • Jesse Roman
    • 1
    • 2
  • ShouWei Han
    • 3
  1. 1.Division of Pulmonary, Allergy and Critical Care Medicine, Department of MedicineEmory University School of MedicineAtlantaUSA
  2. 2.Atlanta Veterans Affairs Medical CenterAtlantaUSA
  3. 3.Division of Endocrinology, Diabetes and Bone Diseases, Department of MedicineMount Sinai School of MedicineNew YorkUSA

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