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Differential Expression of Carotenoid Metabolism Related Genes in Human Lung Epithelial Cells
Author(s) -
Gong Xiaoming,
Marisiddaiah Raju,
Wiener Doris,
Rubin Lewis
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.92.2
Subject(s) - a549 cell , biology , lung cancer , carotenoid , adenocarcinoma , cancer research , gene expression , lycopene , immunohistochemistry , gene , microbiology and biotechnology , cell , cancer , pathology , immunology , biochemistry , genetics , medicine
Epidemiologic studies have demonstrated that dietary beta‐carotene and total carotenoids are inversely associated with non‐small cell lung cancer risk. While high‐dose beta‐carotene supplementation for chronic smokers has been linked to increased lung cancer risk in clinical trials, little is known about the carotenoid metabolomic alterations that characterize neoplastic progression. Using two human pulmonary cell lines, we determined the expression of genes regulating carotenoid metabolism in normal bronchial epithelial (BEAS‐2B) and lung adenocarcinoma pulmonary epithelial (A549) cells. We assayed gene pathways including ALDH1A2, ALDH8A1, CMO1, CMO2, Cyp26A1, Cyp26B1, Cyp26C1, LRAT, RHD5, RHD8, RDH11 ~ 14, RHD16 and SDR16C5 by qRT‐PCR. Our results indicate that carotenoid metabolism‐related genes are expressed as different and distinct patterns in BEAS‐2B and A549 cells. BEAS‐2B cells express high levels of CMO2 and LRAT but not CMO1, Cyp26A1 or Cyp26B1, indicating an active lycopene metabolic apparatus. In contrast, A549 cells highly express CMO1, ALDH1A2, Cyp26A1 and Cyp26B1. In A549 cells, we could detect only low levels of CMO2 and no LRAT expression, implying presence of active beta‐carotene metabolism. We further tested this hypothesis by treating BEAS‐2B and A549 cells with lycopene. CMO2 and LRAT expression were increased but there were no effects on CMO1 expression. Finally, immunohistochemistry of NSCLC tissues shows profuse CMO1 staining in the tumors but little in adjacent normal lung. These findings suggest that specific beneficial effects of carotenoid on lung health may be linked to CMO2‐dependence in tissue. A shift to decreased expression of CMO2 and LRAT and increased CMO1 and Cyp26 family genes can alter carotene metabolism may contribute to lung carcinogenesis. (NIH HD42174, Muma Family Endowment)