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.
Copyright 2004 Elsevier Inc.