State of differentiation affects the response of endometrial adenocarcinoma cells to retinoic acid.

Patients with poorly differentiated endometrial cancers have a worse prognosis than patients with well-differentiated endometrial cancers. If poorly differentiated cells in endometrial cancers could be induced to differentiate, they would be more responsive to hormonal manipulation, and survival rates would be increased. We set up an in vitro model system to examine the effects of retinoic acid on human endometrial adenocarcinoma cells at three states of differentiation. Cells were treated with pharmacological doses of 13-cis or all-trans retinoic acid (0.5 microM, 1 microM or 5 microM), and stained for mucins or actin filaments. Untreated undifferentiated (KLE) cells lack organized actin filaments and cytoplasmic mucins. Treatment with 5 microM retinoic acid caused some reorganization of actin filaments, but cytoplasmic mucins remained absent. Moderately differentiated (RL95-2) cells differentiated the most with retinoic acid treatment evidenced by a dramatic reorganization of actin filaments and an increase in cytoplasmic mucins. Untreated or treated well differentiated (Ishikawa) cells possessed well organized actin filaments and exhibit positive staining for cytoplasmic mucins. Retinoic acid causes cellular differentiation in less differentiated human endometrial adenocarcinoma cells.