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) 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.
Won
Jun Yeon
JY
Department of Otolaryngology, University of Kangwon College of Medicine, Chunchon, South Korea.
Nam
Eui-Cheol
EC
Yoo
Seung Joo
SJ
Kwon
Hyun Ja
HJ
Um
Soo Jong
SJ
Han
Hye Sook
HS
Kim
Sun Hee
SH
Byun
Youngro
Y
Kim
Sang Yoon
SY
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D002855:Chromatography, Thin Layer; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D015500:Chloramphenicol O-Acetyltransferase