This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Pinpin Lin Articles by Su, J.-M. Search for Related Content PubMed PubMed Citation Articles by Pinpin Lin, Articles by Su, J.-M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Lung Cancer Social Bookmarking                         What's this?

Overexpression of Aryl Hydrocarbon Receptor in Human Lung Carcinomas

Institute of Toxicology, Chung-Shan Medical University, Taichung, Taiwan, ppl{at}csmu.edu.tw

Han Chang

Department of Pathology, Chung-Shan Medical University Hospital, Taichung, Taiwan

Wen-Tin Tsai

Institute of Toxicology, Chung-Shan Medical University, Taichung, Taiwan

Meng-Hsiang Wu

Institute of Toxicology, Chung-Shan Medical University, Taichung, Taiwan

Yung-Shen Liao

Institute of Toxicology, Chung-Shan Medical University, Taichung, Taiwan

Jung-Ta Chen

Department of Pathology, Veterans General Hospital-Taichung, Taiwan

Jang-Ming Su

Division of Thoracic Surgery, Department of Surgery, Chung-Shan Medical University Hospital, Taichung, Taiwan

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.

Key Words: Aryl hydrocarbon receptor • lung carcinoma • overexpression • adenocarcinoma.

References

• Anttila S., Hietanen E., Vainio H., Camus A-M., Gelboin HV, Park SS, Heikkila L., Karjalainen A., Bartsch H. (1991). Smoking and peripheral type of cancer are related to high levels of pulmonary cytochrome P4501A in lung cancer patients. Int J Cancer 47: 681—685.[Web of Science][Medline] [Order article via Infotrieve]
• Barbone F., Bovenzi M., Cavallieri F., Stanta G. (1997). Cigarette smoking and histologic type of lung cancer in men. Chest I 12: 1474— 1479.
• Boffetta P., Jourenkova N., Gustavsson P. (1997). Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. Cancer Causes Control 8: 444—472.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Chang KW, Lee H., Wang HJ, Chen SY, Lin P. (1999). Differential response to benzo[a]pyrene in human lung adenocarcinoma cell lines: The absence of aryl hydrocarbon receptor activation. Life Sci 65: 1339— 1349.
• Department of Health, the Executive Yuan ( 1998). Republic of China: General Health Statistics. Health and Vital Statistics, Republic of China. ROC Press, Taipei, pp 82—89.
• De Vries A., Dolle ME, Broekhof JL, Muller JJ, Kroese ED, Kreijl CF, Capel PJ, Vijg J., Steeg H. (1997). Induction of DNA adducts and mutations in spleen, liver and lung of XPA-deficient/lacZ transgenic mice after oral treatment with benzo[a]pyrene: Correlation with tumour development. Carcinogenesis 18: 2327—2332.[Abstract/Free Full Text]
• Fernandez-Salguero PM, Hilbert DM, Rudikoff S., Ward JM, Gonzalez FJ (1996). Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducedtoxicity. ToxicolApplPharmacol 140: 173—179.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Gazdar AF, Minna JD (1997). Cigarettes, sex, and lung adenocarcinoma. J Natl Cancer Inst 89: 1563—1565.[Free Full Text]
• Hayashi S-I., Watanabe J., Nakachi K., Eguchi H., Gotoh O., Kawajiri K. (1994). Interindividual difference in expression of human Ah receptor and related P450 genes. Carcinogenesis 15: 801—806.[Abstract/Free Full Text]
• Hayes CL, Spink DC, Spink BC, Cao JQ, Walker NJ, Sutter TR (1996). 17β estradiol hydroxylation catalyzed by human cytochrome P4501B1. Proc Natl Acad Sci USA 93: 9776—9781.[Abstract/Free Full Text]
• Hsu JW, Hsu SL, Chu JJ, Liu MC, Chiang CD (1997). Increased NM23:MTS1 ratio inversely correlated with metastasis behaviour in human lung squamous cell carcinoma. Anticancer Res 17: 407—411.[Web of Science][Medline] [Order article via Infotrieve]
• Iwagawa M., Maeda T., Izumi K., Otsuka H., Nishifuji K., Ohnishi Y., Aoki S. ( 1989). Comparative dose-response study on the pulmonary carcinogenicity of 1,6-dinitropyrene and benzo[a]pyrene in F344 rats. Carcinogenesis 10: 1285—1290.[Abstract/Free Full Text]
• Kashani M., Steiner G., Haitel A., Schaufler K., Thalhammer T., Amann G., Kramer G., Marberger M., Scholler A. (1998). Expression of the aryl hydrocarbon receptor (AhR) and the aryl hydrocarbon receptor nuclear translocator (ARNT) in fetal, benign, hyperplastic and malignant prostate. Prostate 37: 98—108.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kellermann G., Shaw CR, Luyten-Kellermann M. (1973). Aryl hydrocarbon hydroxylase inducibility and bronchogenic carcinoma. N Eng J Med 263: 131—133.
• Kociba RJ, Keyes DG, Beyer JE, Carreon RM, Wade CE, Dittenber DA, Kalnins RP, Frauson LE, Park CN, Barnard SD, Hummel RA, Humiston CG (1978). Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol Appl Pharmacol 46: 279—303.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kogevinas M. (2000). Studies of cancer in humans. Food Addit Contamin 17: 317—324.[CrossRef]
• Kouri RE, McKinney CE, Slomiany DJ, Snodgrass DR, Wray NP, McLemore TL (1982). Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res 42: 5030—5037.[Abstract/Free Full Text]
• Kress S., Greenlee WF (1997). Cell-specific regulation of human CYP1A1 and CYP1B1 genes. Cancer Res 57: 1264—1269.[Abstract/Free Full Text]
• Lee TC, Ho IC (1994). Expression of heme oxygenase in arsenic-resistant human lung adenocarcinoma cells. Cancer Res 54: 1660—1664.[Abstract/Free Full Text]
• Lin P., Wang SL, Wang HJ, Chen KW, Lee HS, Tsai KJ, Chen CY, Lee H. (2000). Association of CYP1A1 and microsomal epoxide hydrolase polymorphisms with lung squamous cell carcinoma. J Cancer 82: 852— 857.
• Murray GI, Taylor MC, McFayden MCE, McKay JA, Greenlee WF, Burke MD, Melvin WT (1997). Tumor-specific expression of cytochrome P4501B1. Cancer Res 57: 3026—3031.[Abstract/Free Full Text]
• Osann KE (1998). Epidemiology of lung cancer. Current Opin Pulmon Med 4: 198—204.[Medline] [Order article via Infotrieve]
• Pisani P., Parkin DM, Bray F., Ferlay J. (1999). Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83: 18029.
• Prasad R., Prasad N., Harrell JE, Thornby J., Liem JH, Hudgins PT, Tsuang J. (1979). Aryl hydrocarbon hydroxylase inducibility and lymphoblast formation in lung cancer patients. Int J Cancer 23: 316—320.[Web of Science][Medline] [Order article via Infotrieve]
• Rowlands JC, Gustafsson JK (1997). Aryl hydrocarbon receptor-mediated signal transduction. Crit Rev Toxicol 27: 109—134.[Web of Science][Medline] [Order article via Infotrieve]
• Saarikoski S., Husgafvel-Pursiainen K., Hirvonen A., Vainio H., Gonzalez FJ, Anttila S. (1998). Localization of CYP1A1 mRNA in human lung by in situ hybridization: Comparison with immunohistochmical findings. Int J Cancer 77: 33—39.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Shimada T., Hayes CL, Yamazaki H., Amin S., Hecht SS, Guengerich FP (1996). Activation of chemically diverse procarcinogens by human cytochrome P4501B1. Cancer Res 56: 2979—2984.[Abstract/Free Full Text]
• Shimada T., Yun CH, Yamazaki H., Gautier JC, Beaune PH, Guengerich FP (1992). Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens. Mol Pharmacol 41: 856—864.[Abstract]
• Shimizu Y., Nakatsuru Y., Ichinose M., Takahashi Y., Kume H., Mimura J., Fujii-Kuriyama Y., Ishikawa T. (2000). Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 97: 779—782.[Abstract/Free Full Text]
• Spivack SD, Hurteau GJ, Reilly AA, Aldous KM, Ding X., Kaminsky LS (2001). CYP1B1 expression in human lung. Drug Metab Dispos 29: 916— 922.
• Stucker I., Jacquet M., De Waziers I., Cenee S., Beaune PH, Kremers P., Hemon D. (2000). Relation between inducibility of CYP1A1, GSTM1 and lung cancer in a French population. Pharmacogenentics 10: 617—627.[CrossRef]
• Tritscher AM, Mahler J., Portier CJ, Lucier GW, Walker NJ (2000). Induction of lung lesions in female rats following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Pathol 28: 761—769.[Abstract/Free Full Text]
• Trombino AF, Near RI, Matulka RA, Yang S., Hafer LJ, Toselli PA, Kim DW, Rogers AE, Sonenshein GE, Sherr DH (2000). Expression of the aryl hydrocarbon receptor/transcription factor (AhR) and AhR-regulated CYP1 gene transcripts in a rat model of mammary tumorigenesis. Breast Cancer Res Treat 63: 117—131.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Wang HW, Chen TL, Yang PC, Ueng TH ( 2001). Induction of cytochromes P450 1A1 and 1B1 by emodin in human lung adenocarcinoma cell line CL5. Drug Metab Dispos 29: 1229—1235.[Abstract/Free Full Text]
• Ward E., Paigen B., Steenland K., Vincent R., Minowada J., Gurtoo HL, Sartori P., Havens MB (1978). Aryl hydrocarbon hydroxylase in persons with lung or laryngeal cancer. Int J Cancer 22: 384—389.[Web of Science][Medline] [Order article via Infotrieve]
• Whitlock Jr JP (1999). Induction of cytochrome P4501A1. Ann Rev Pharmacol Toxicol 39: 103—125.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 31, No. 1, 22-30 (2003)
DOI: 10.1080/01926230390173824


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Pinpin Lin Articles by Su, J.-M. Search for Related Content PubMed PubMed Citation Articles by Pinpin Lin, Articles by Su, J.-M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Lung Cancer Social Bookmarking                         What's this?