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Molecular Pharmacology

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Research ArticleArticle

Induction of the Cytochrome P450 Gene CYP26 during Mucous Cell Differentiation of Normal Human Tracheobronchial Epithelial Cells

Seong Yong Kim, Hiroshi Adachi, Ja Seok Koo and Anton M. Jetten
Molecular Pharmacology September 2000, 58 (3) 483-490; DOI: https://doi.org/10.1124/mol.58.3.483
Seong Yong Kim
Cell Biology Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
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Hiroshi Adachi
Cell Biology Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
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Ja Seok Koo
Cell Biology Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
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Anton M. Jetten
Cell Biology Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
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Abstract

In this study, the expression of CYP26 is examined in relation to retinoid-induced mucosecretory differentiation in human tracheobronchial epithelial (HTBE) cells and compared with that in human lung carcinoma cell lines. In HTBE cells, retinoic acid (RA) inhibits squamous differentiation and induces mucous cell differentiation as indicated by the suppression of transglutaminase I and increased expression of the mucin gene MUC2. The latter is accompanied by increased expression of CYP26 mRNA. RA is required but not sufficient to induce RARβ, CYP26, and MUC2 mRNA because induction is only observed in confluent but not in logarithmic cultures, suggesting that additional factors are critical in their regulation. CYP26 mRNA can be induced by the RAR-selective retinoid 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)-benzoic acid (TTAB) but not by the RXR-selective retinoid SR11217 or the anti-activator-protein 1-selective retinoid SR11302. RARα-, β-, and γ-selective retinoids are able to induce CYP26; this induction is inhibited by the RARα-selective antagonist Ro41-5253. TTAB is able to induce CYP26 mRNA expression in only a few of the lung carcinoma cell lines tested. The lack of CYP26 induction in many carcinoma cell lines may relate to previously reported defects in the retinoid-signaling pathway. The induction of CYP26 correlated with increased metabolism of RA into 18-hydroxy-, 4-oxo-, and 4-hydroxy-RA. The latter metabolite was shown to be able to induce MUC2 and MUC5AC expression in HTBE cells. Our results demonstrate that in normal HTBE cells, CYP26 expression is closely associated with mucous cell differentiation and that many lung carcinoma cells exhibit increased RA metabolism and a defective regulation of CYP26.

Footnotes

    • Received April 4, 2000.
    • Accepted June 12, 2000.
  • Send reprint requests to: Dr. Anton M. Jetten, Cell Biology Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina. E-mail: jetten{at}niehs.nih.gov

  • ↵1 Current address: Department of Biochemistry, College of Medicine, Yeungnam University, Daegu, Korea.

  • U.S. Government
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Molecular Pharmacology: 58 (3)
Molecular Pharmacology
Vol. 58, Issue 3
1 Sep 2000
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Research ArticleArticle

Induction of the Cytochrome P450 Gene CYP26 during Mucous Cell Differentiation of Normal Human Tracheobronchial Epithelial Cells

Seong Yong Kim, Hiroshi Adachi, Ja Seok Koo and Anton M. Jetten
Molecular Pharmacology September 1, 2000, 58 (3) 483-490; DOI: https://doi.org/10.1124/mol.58.3.483

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Research ArticleArticle

Induction of the Cytochrome P450 Gene CYP26 during Mucous Cell Differentiation of Normal Human Tracheobronchial Epithelial Cells

Seong Yong Kim, Hiroshi Adachi, Ja Seok Koo and Anton M. Jetten
Molecular Pharmacology September 1, 2000, 58 (3) 483-490; DOI: https://doi.org/10.1124/mol.58.3.483
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