Abstract 1861: PPAR γ mediated involucrin induction in aerodigestive preneoplasia in vitro

Abstract

Abstract Effective prevention and monitoring of head and neck malignancy is a critical component of disease control which is significantly underdeveloped. Currently, no validated biomarkers or therapies for human aerodigestive preneoplasia exist. We have increasing interest in PPARγ mediated therapy for oral leukoplakia reversal based on our preliminary clinical trial results. Involucrin expression is associated with squamous differentiation and we hypothesize involucrin would be involved with PPARγ upregulation in differentiation therapies. In our present study we examined the use of involucrin as marker of PPARγ activity in response to treatment and effect of bexarotene on pioglitazone mediated PPARγ activation in oral leukoplakia. In an analysis of an Affymetrix database of human head and neck tumors (41 tumors compared to 13 normal oral mucosa samples), we found involucrin is expressed 5.6fold higher in normal versus tumor samples (P<0.0001). We found pioglitazone upregulates PPARγ DNA binding activity and involucrin promoter activity via reporter gene assay. Bexarotene positively effects pioglitazone upregulation of these genes via reporter gene assay and increases protein expression via western blot analysis We conclude the PPARγ activator, pioglitazone, can activate involucrin, which may be useful in upregulating differentiation in oral preneoplasia in clinical trialsin combination with bexarotene. Also involucrin has potential use as a biomarker of disease response to treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1861. doi:10.1158/1538-7445.AM2011-1861