ALL-TRANS-RETINOIC ACID-INDUCED GENE-EXPRESSION AND GROWTH-INHIBITIONIN HEAD AND NECK-CANCER CELL-LINES

Retinoids are natural and synthetic analogues of vitamin A and have pr oven activity in various types of cancer. As far head and neck squamou s cell cancer (HNSCC), retinoids are especially active in leukoplakia and in preventing second primary cancers. The aim of this study was to assess the growth inhibiting activity of all-trans retinoic acid (all -trans RA) in a panel of six head and neck squamous cell cancer cell l ines and to correlate this response to the mRNA expression of factors related to differentiation and receptor mediated signal transduction. Three lines showed minimal, two moderate and one strong growth inhibit ion after 72 h exposure to all-trans RA. Three Lines with a dissimilar response were selected for further studies, the measurement of mRNA e xpression by northern blotting. It was found that neither the expressi on nor the induction of retinoic acid receptor (RAR)-alpha and -gamma and retinoic X receptor-alpha mRNA was related to sensitivity. The mRN A expression of RAR-beta was too low to be measured in the three cell lines. The most sensitive cell line was, however, the only one that ex pressed mRNA of squamous differentiation markers. These data suggest a relationship between the retinoid sensitivity profile and the degree of cellular differentiation. (C) 1997 Elsevier Science Ltd.