title: The loss of retinoic acid receptor alpha, beta and alcohol dehydrogenase3 expression in non-small cell lung cancer.
abstract: 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.
  
  
  METHODS
  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 alpha, beta, gamma, retinoid X receptor alpha, beta, gamma, thyroid hormone receptor alpha, beta, 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) reducion in retinoic acid receptor alpha and beta 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 beta-mRNA level and the alcohol dehydrogenase3-mRNA level (r = 0.52, P < 0.05). In situ hybridization and immunostaining demonstrated that retinoic acid receptor alpha and beta 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 beta mRNA in BEAS-2B cells (P < 0.05).
  
  
  CONCLUSIONS
  The present findings suggest a possible association of the loss of retinoic acid receptor alpha, beta and alcohol dehydrogenase3 with lung carcinogenesis.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Sasaki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects; D013638:Tars / Q000378:metabolism
chemical_list: C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000072482:Retinoic Acid Receptor alpha; D013638:Tars; C082925:retinoic acid receptor beta; C024746:tobacco tar; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases