The effect of cellular retinoic acid binding protein-I expression on the CYP26-mediated catabolism of all- trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma

The aim of this study was to confirm if catabolism of all- trans retinoic acid (RA) is enhanced by type I cellular retinoic acid binding protein (CRABP-I) expression and to investigate the effect of this enhanced catabolism on cell proliferation of the head and neck squamous cell carcinoma (HNSCC) c...

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Veröffentlicht in:Metabolism, clinical and experimental clinical and experimental, 2004-08, Vol.53 (8), p.1007-1012
Hauptverfasser: Won, Jun Yeon, Nam, Eui-Cheol, Yoo, Seung Joo, Kwon, Hyun Ja, Um, Soo Jong, Han, Hye Sook, Kim, Sun Hee, Byun, Youngro, Kim, Sang Yoon
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container_end_page 1012
container_issue 8
container_start_page 1007
container_title Metabolism, clinical and experimental
container_volume 53
creator Won, Jun Yeon
Nam, Eui-Cheol
Yoo, Seung Joo
Kwon, Hyun Ja
Um, Soo Jong
Han, Hye Sook
Kim, Sun Hee
Byun, Youngro
Kim, Sang Yoon
description The aim of this study was to confirm if catabolism of all- trans retinoic acid (RA) is enhanced by type I cellular retinoic acid binding protein (CRABP-I) expression and to investigate the effect of this enhanced catabolism on cell proliferation of the head and neck squamous cell carcinoma (HNSCC) cell line, AMC-HN-7. We also analyzed the effects of CRABP-I on RA-induced retinoic acid receptor (RAR) activity. The expression of the CRABP-I in stably transfected AMC-HN-7 cell lines (HN7-BPIa and HN7-BPIb) resulted in a lower sensitivity to administered RA compared with that of controls in a clonogenic assay. HN7-BPIs cells showed an increased amount of polar metabolites of RA in thin-layer chromatography. The transcriptional activity of the reporter plasmid RARE(DR5)-tk-CAT after the treatment of RA was lesser in HN7-BPIs than in controls. These results suggest that the increased CYP26-mediated catabolism of RA by CRABP-I transfection might decrease the amount of RA that is accessible to the nuclear receptors and make HNSCC cells resistant to RA.
doi_str_mv 10.1016/j.metabol.2003.12.015
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We also analyzed the effects of CRABP-I on RA-induced retinoic acid receptor (RAR) activity. The expression of the CRABP-I in stably transfected AMC-HN-7 cell lines (HN7-BPIa and HN7-BPIb) resulted in a lower sensitivity to administered RA compared with that of controls in a clonogenic assay. HN7-BPIs cells showed an increased amount of polar metabolites of RA in thin-layer chromatography. The transcriptional activity of the reporter plasmid RARE(DR5)-tk-CAT after the treatment of RA was lesser in HN7-BPIs than in controls. 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We also analyzed the effects of CRABP-I on RA-induced retinoic acid receptor (RAR) activity. The expression of the CRABP-I in stably transfected AMC-HN-7 cell lines (HN7-BPIa and HN7-BPIb) resulted in a lower sensitivity to administered RA compared with that of controls in a clonogenic assay. HN7-BPIs cells showed an increased amount of polar metabolites of RA in thin-layer chromatography. The transcriptional activity of the reporter plasmid RARE(DR5)-tk-CAT after the treatment of RA was lesser in HN7-BPIs than in controls. These results suggest that the increased CYP26-mediated catabolism of RA by CRABP-I transfection might decrease the amount of RA that is accessible to the nuclear receptors and make HNSCC cells resistant to RA.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15281009</pmid><doi>10.1016/j.metabol.2003.12.015</doi><tpages>6</tpages></addata></record>
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subjects Biological and medical sciences
Blotting, Western
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Division - physiology
Chloramphenicol O-Acetyltransferase - metabolism
Chromatography, Thin Layer
Cytochrome P-450 Enzyme System - metabolism
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - pathology
Humans
Medical sciences
Otorhinolaryngology (head neck, general aspects and miscellaneous)
Otorhinolaryngology. Stomatology
Receptors, Retinoic Acid - biosynthesis
Receptors, Retinoic Acid - genetics
Retinoic Acid 4-Hydroxylase
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Tretinoin - metabolism
Tumor Stem Cell Assay
Tumors
title The effect of cellular retinoic acid binding protein-I expression on the CYP26-mediated catabolism of all- trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma
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