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PPARbeta/delta agonist increases the expression of PGE2 receptor subtype EP4 in human lung carcinoma cells

Jeffrey D Ritzenthaler1, Jesse Roman, ShouWei Han

  • 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Methods in Molecular Biology (Clifton, N.J.)
|April 7, 2009
PubMed

Insights

Activation of Peroxisome proliferator-activated receptor beta/ delta (PPARbeta/delta) stimulates non-small cell lung carcinoma (NSCLC) growth by increasing prostaglandin E(2) receptor EP4. This discovery offers a novel target for lung cancer drug discovery.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Lung carcinoma, particularly non-small cell lung carcinoma (NSCLC), has a poor prognosis despite therapeutic advances.
  • Prostaglandin E(2) (PGE(2)) and its receptor EP4 are implicated in promoting NSCLC growth and progression.
  • Peroxisome proliferator-activated receptor beta/ delta (PPARbeta/delta) is a nuclear receptor involved in tumorigenesis.

Purpose of the Study:

  • To investigate the role of PPARbeta/delta in NSCLC proliferation.
  • To determine if PPARbeta/delta activation influences EP4 expression and activity.
  • To elucidate the molecular mechanism by which PPARbeta/delta affects NSCLC growth.

Main Methods:

  • Analysis of PPARbeta/delta protein expression in NSCLC cells.
  • Treatment of NSCLC cells with a selective PPARbeta/delta agonist (GW501516).
  • Assessment of EP4 expression, EP4 promoter activity, and NSCLC cell proliferation.
  • Investigation of transcription factor binding to the EP4 promoter.

Main Results:

  • NSCLC cells express PPARbeta/delta protein.
  • Treatment with the PPARbeta/delta agonist GW501516 increased EP4 expression and stimulated NSCLC cell proliferation.
  • GW501516 enhanced EP4 promoter activity via C/EBP binding to the NF-IL6 site.
  • PPARbeta/delta activation directly influences cancer cell growth.

Conclusions:

  • PPARbeta/delta activation is a novel mechanism regulating human lung cancer cell growth.
  • Targeting the PPARbeta/delta pathway may offer a new therapeutic strategy for NSCLC.
  • Understanding the interaction between PPARbeta/delta and EP4 is crucial for developing effective lung cancer treatments.

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