Effects of Retinoic Acid on Differentiation of Choriocarcinoma Cells in Vitro*

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Abstract
Choriocarcinoma cells maintain multiple hormonal functions in culture. We have found that these cells secreted no immunoreactive pregnancy-specific β1-glycoprotein (PSβG), a placental protein. Choriocarcinoma cells can be induced to synthesize low levels of PSβG by retinoic acid, 8-bromocAMP (8BrcAMP), cholera toxin, methyl-isobutylxanthine (MIX), and 5-bromo-2′-deoxyuridine (BrdUrd). The simultaneous addition of retinoic acid along with 8BrcAMP, cholera toxin, or MIX gave synergistic induction of PSβG. The simultaneous addition of retinoic acid and BrdUrd failed to give even additive induction. In addition to stimulating PSβG production, retinoic acid increased the production of hCG and its a-subunit (hCGα) by choriocarcinoma cells. The simultaneous addition of retinoic acid along with 8BrcAMP, cholera toxin, or MIX gave additive induction for hCG and hCGα. Passage of choriocarcinoma cells in medium containing retinoic acid induced a stable altered phenotype characterized by elevated levels of PSβG, hCG, and hCGα. These retinoid-treated choriocarcinoma cells remained responsive to 8BrcAMP or compounds that increase intracellular cAMP concentrations and to BrdUrd; the production of PSβG and hCG was greatly stimulated by 8BrcAMP, cholera toxin, or MIX, and the production of hCG and hCGα was greatly inhibited by BrdUrd. However, the production of hCGa was only slightly induced by these cAMP modulators, and the production of PSβG was not increased by BrdUrd. (J Clin Endocrinol Metab54: 1174, 1982)