Cyclopentenone 15-Deoxy-D^12-14 -PGJ2 Inhibits Transforming Growth Factor Alpha/Epidermal Growth Factor Receptor Signaling in Human Oral Squamous Carcinoma Cell Lines

Up-regulation and autocrine activation of the TGF-a/EGFR pathway has been implicated in cell proliferation and survival of head and neck cancer. We previously reported that treatment with cyclopentenone 15-deoxy-D^12-14-PGJ2 (15-dPGJ2) induces cell cycle arrest and apoptosis in human oral squamous cell carcinoma (SCC) lines and that treatment with other ligands of peroxisome proliferator-activated receptor gamma (PPAR-g) do not mimic these effects. Objective: In this study, we examined the specific effects of 15-dPGJ2 on the expression of EGFR and assessed its role in TGF-a-mediated activation of EGFR. Methods: Four established human oral SCC cell lines (SCC4, 9, 15 and 25) were treated with 15-dPGJ2, or the PPAR-g synthetic ligands, ciglitazone and rosiglitazone. EGFR protein phosphorylation and expression were determined by immunoprecipitation and western blot analysis. The mRNA levels of EGFR were assessed by Real-Time quantitative RT-PCR. Results: Treatment with 15-dPGJ2, and not other PPAR-g ligands, abrogates protein expression and phosphorylation of EGFR in a time-dependent manner. No changes in EGFR mRNA levels were observed. Conclusion: These results suggest that the growth inhibitory effects of the 15-dPGJ2 may be in part mediated by interfering with TGF-a/EGFR signaling pathway. (Supported by NIH DE12606 and DE13118)