Overexpression of Aryl Hydrocarbon Receptor in Human Lung Carcinomas

Abstract

Exposure to polycylic aromatic hydrocarbons (PAH) has been associated with increased risk of lung cancer. Aryl hydrocarbon receptor (AhR) is known to play an essential role in PAH-induced toxicity. The objectives of this study were to identify and evaluate AhR expression in normal human lung tissues and in lung carcinomas. AhR protein and mRNA levels in human lung cell lines were evaluated with immunoblot and quantitative real-time RT-PCR assays, respectively. AhR protein expression was high in cytosol homogenates of adenocarcinoma (AD) cell lines and AhR mRNA levels corresponded well with AhR protein levels in these cell lines. AhR expression in human lung tissues and carcinomas were examined by means of immunohistochemical staining method. In normal lung tissues, immunostaining was found in the cytosol of bronchiolar epithelial cells. AhR immunostaining was more intense in AD than in squamous cell carcinomas. When AhR expression was compared with normal bronchiolar epithelial cells and neoplastic cells in the same specimens, the neoplastic cells, especially those of AD, demonstrated an increased staining. The upregulation of AhR mRNA expression was also demonstrated among 2 of 4 paired tissues with the quantitative real-time RT-PCR assay. Our data indicated that AhR expression was upregulated in lung AD and suggested that AhR and its expression might play an important role in the development of lung AD.