All-trans-retinoic acid (RA) is a powerful differentiation-inducing reagent. We examined the effect of RA on malignant phenotype of human lung adenocarcinoma cell line GLC-82 in vitro. Treatment of GLC-82 cell with 10(-5)mol/L. RA for 1-7 days resulted in suppression of cell proliferation (33-55%), inhibition of colony formation in soft agar (97.5%), and a decrease of 3H-TdR incorporation (30-60%). Cytokinetic studies demonstrated that the cells arrested in G1/G0 phase increased from 36.0% to 72.4%, which is typical for cell differentiation. Human endothelial cell transglytaminase (TGase) was expressed persistently during RA treatment. Treatment of GLC-82 cell with RA gave rise to senescence and apoptosis gradually. The results indicated that induction of differentiation and modulation of gene expression can be achieved by RA treatment in human lung adenocarcinoma cell line GLC-82.