EFFECTS OF RETINOIC ACID ON CELL-DIFFERENTIATION AND REVERSION TOWARDNORMAL IN HUMAN ENDOMETRIAL ADENOCARCINOMA (RL95-2) CELLS

Background: All-trans retinoic acid is currently used in clinical tria ls in combination with tamoxifen to treat breast cancer, and 13-cis re tinoic acid is used with a-interferon to treat metastatic endometrial cancer. We examined the effects of all-trans retinoic acid 13-cis RA a lone on endometrial adenocarcinoma (RL95-2) cells to investigate the c ell biological mechanisms by which retinoic acid may reduce the metast atic phenotype and induce differentiation. Methods: RL95-2 cells were seeded onto 4-chamber plastic slides and treated with 13-cis retinoic acid or all-trans retinoic acid at 0.5 mu M, 1 mu M and 5 mu M doses f or 90 minutes at 37 degrees C and stained for F-actin. Results: Untrea ted RL95-2 cells exhibited staining of disrupted aggregates of F-actin only near the cell periphery. Cells treated with the three doses of 1 3-cis retinoic acid exhibited a dramatic reorganization of F-actin thr oughout the cells. When cells were treated with 0.5 mu M all-trans ret inoic acid, actin filaments reorganized. Cells treated with 1 mu M all -trans retinoic acid and 5 mu M all-trans retinoic acid displayed incr eased organization of F-actin and cell size increased. The percentage of S-phase cells increased at the high doses of retinoic acid treatmen t. This effect was apparently transient, since retinoic acid did not s ignificantly affect cell growth. Conclusion: An organized cytoskeleton and an increase in cell size are associated with differentiation. We suggest that retinoic acid exerts its effects on these transformed cel ls by reorganizing actin filaments, and inducing differentiation, thus inducing a more stationary phenotype.