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The loss of retinoic acid receptor α, β and alcohol dehydrogenase3 expression in non‐small cell lung cancer
Author(s) -
INUI Naoki,
SASAKI Shigekazu,
SUDA Takafumi,
CHIDA Kingo,
NAKAMURA Hirotoshi
Publication year - 2003
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1046/j.1440-1843.2003.00481.x
Subject(s) - retinoid x receptor gamma , retinoic acid , retinoic acid receptor beta , retinoid x receptor alpha , retinoic acid receptor alpha , retinoic acid receptor , retinoid x receptor beta , immunostaining , retinoid , receptor , in situ hybridization , cancer research , retinoid x receptor , medicine , retinoic acid receptor gamma , endocrinology , receptor expression , microbiology and biotechnology , biology , gene expression , immunohistochemistry , cell culture , nuclear receptor , biochemistry , gene , transcription factor , genetics
Objective: The reason for unsuccessful retinoid chemoprevention of lung cancer is obscure. Therefore we examined the retinoid‐related receptor expression and the tissue distribution as well as the possible interaction between retinoid‐related receptor expression and cigarette smoke. Methodology: Using semiquantitative conventional reverse transcriptase polymerase chain reaction (RT‐PCR), quantitative real‐time RT‐PCR, in situ hybridization and immunostaining, we evaluated the expression and the distribution of retinoic acid receptor α, β, γ, retinoid X receptor α, β, γ, thyroid hormone receptor α, β, and alcohol dehydrogenase3 (a well‐characterized retinoic acid responsive gene) in malignant and non‐malignant tissues obtained from patients with non‐small cell lung cancer. We also assessed the response of the bronchial epithelial cell line, BEAS‐2B, following exposure to cigarette smoke extract. Results: Compared with non‐malignant tissues, malignant tissues had a 45% ( P < 0.02) redution in retinoic acid receptor α and β expression, while other receptors were not affected. The expression of the alcohol dehydrogenase3 gene in malignant tissue was 50% of that observed in non‐malignant tissue ( P < 0.05). There was a significant correlation between the retinoic acid receptor β‐mRNA level and the alcohol dehydrogenase3‐mRNA level ( r = 0.52, P < 0.05). In situ hybridization and immunostaining demonstrated that retinoic acid receptor α and β were localized in the airway and alveolar epithelial cells and their expression was diminished to 30% in malignant tissues compared to non‐malignant tissues ( P < 0.05). Interestingly, cigarette smoke extract decreased retinoic acid receptor β mRNA in BEAS‐2B cells ( P < 0.05). Conclusions: The present findings suggest a possible association of the loss of retinoic acid receptor α, β and alcohol dehydrogenase3 with lung carcinogenesis.