Identification of Pro‐Differentiation Patterns by Gene Expression Analysis following Pioglitazone Treatment in a Primary Laryngeal Tumor Cell Line

Abstract

Head and neck squamous cell carcinoma (HNSCC) affects nearly 500,000 individuals worldwide each year, with nearly 40,000 patients in the US alone. The 5-year survival rate is approximately 50%, and has not improved significantly in the past 20 years despite extensive efforts to increase cure rates. As such, there exists a need for safe therapeutics to improve survival. Recent efforts have turned toward chemopreventative measures to fulfill this need. The peroxisome proliferator-activated receptor γ (PPARγ), initially investigated for its role in adipocyte differentiation, has pro-apoptotic and antiangiogenic effects as well, leading to interest in the use of PPARγ agonists for cancer treatment. A non-randomized phase II clinical trial at the U of MN demonstrated pioglitazone (Actos®), a PPARγ agonist of the thiazolidinedione (TZD) drug class which is FDA approved for diabetes, clinically reduced preneoplastic leukoplakia lesions which often lead to HNSCC. An additional recent study from the U of MN utilized microarrays to analyze the extent to which differential gene modulation occurs in tumor vs. non-tumor human oral squamous cells and elucidate a gene expression profile reflective of tumorigenesis. However, no study has yet been performed which attempts to specifically analyze differential gene expression between normal, tumor, and pioglitazone-treated tumor cells on a genome-wide basis. This analysis serves as a pilot project to assess the feasibility of such a study. Identification of Pro-Differentiation Patterns by Gene Expression Analysis following Pioglitazone Treatment in a Primary Laryngeal Tumor Cell Line Nathan R. Handley1, Patrick M. Gaffney2, Randall S. Taylor3, Beverly R. Wuertz1, and Frank G. Ondrey1 1Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, MN 2Oklahoma Medical Research Foundation, Oklahoma City, OK, 3Comprehensive ENT, Littleton, CO