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 suuamous cell carcinoma

The aim of this study was to confirm if catabolism of all-trans retinoic acid (RA) is enhanced by type 1 cellular retinoic acid binding protein (CRABP-1) 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-1 on RA-induced retinoic acid receptor (RAR) activity. The expression of the CRABP-1 in stably transfected AMC-HN-7 cell lines (HN7-BPIa and HN7-BP1b) 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-1 transfection might decrease the amount of RA that is accessible to the nuclear receptors and make HNSCC cells resistant to RA. (C) 2004 Elsevier Inc. All rights reserved.