STATE OF DIFFERENTIATION AFFECTS THE RESPONSE OF ENDOMETRIAL ADENOCARCINOMA CELLS TO RETINOIC ACID

Background: Patients with poorly differentiated endometrial cancers ha ve a worse prognosis than patients with well-differentiated endometria l cancers. If poorly differentiated, cells in endometrial cancers coul d be induced to differentiate, they would be more responsive to hormon al manipulation, and survival rates would be increased. We set up an i n vitro model system to examine the effects of retinoic acid on human endometrial adenocarcinoma cells at three states of differentiation. M ethods: Cells were treated with pharmacological doses of 23-cis or all -trans retinoic acid (0.5 mu M, 1 mu M or 5 mu M), and stained for muc ins or actin filaments. Results: Untreated undifferentiated (KLE) cell s lack organized actin filaments and cytoplasmic mucins. Treatment wit h 5 mu M retinoic acid caused some reorganization of actin filaments, but cytoplasmic mucins remained absent. Moderately differentiated (RL9 5-2) cells differentiated the most with retinoic acid treatment eviden ced by a dramatic reorganization of actin filaments and an increase in cytoplasmic mucins. Untreated or treated well differentiated (Ishikaw a) cells possessed well organized actin filaments and exhibit positive staining for cytoplasmic mucins. Conclusion: Retinoic acid causes cel lular differentiation in less differentiated human endometrial adenoca rcinoma cells.