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Stimulation of Synthesis and Secretion of Chorionic Gonadotropin Subunits by Eutopic and Ectopic Hormone-producing Human Cell Lines¹

Biological Markers Program, National Cancer Institute, Frederick Cancer Research Center, Frederick, Maryland 21701

The effects of dibutyryl cyclic adenosine 3'3':-5'-monophosphate (AMP) and sodium butyrate on the synthesis and secretion of human chorionic gonadotropin (HCG) by trophoblastic and nontrophoblastic human cell lines were studied by radioimmunoassay and pulse-chase labeling techniques. Dibutyryl cyclic AMP stimulated synthesis and secretion of HCG- and HCG-ß subunits by the trophoblastic cell lines JAR and BeWo, whereas butyrate had no effect or decreased secretion. On the other hand, a number of nontrophoblastic cell lines (including the breast carcinoma lines ZR-75-31, BT-20, and MCF-7; the bronchogenic carcinoma line ChaGo; and the cervical carcinoma line HeLa S₃) were induced to synthesize and secrete increased amounts of HCG subunits by butyrate, but dibutyryl cyclic AMP had less or no stimulatory effect. The nontrophoblastic brain tumor line CBT was an exception to this general rule in that HCG-ß production was stimulated by dibutyryl cyclic AMP but not by butyrate. In all cases, the drug-induced increase in HCG subunit secretion was directly proportional to the elevation of HCG subunit synthesis. These data suggest that the differential effects of dibutyryl cyclic AMP and butyrate on trophoblastic and nontrophoblastic cells reflect differences in the transcription or translation of HCG subunit genes induced by these agents in the two cell types.

¹ Research supported by the National Cancer Institute under Contract N01-CO-75380 with Litton Bionetics, Inc.

² To whom requests for reprints should be addressed.

Received 4/ 7/80. Accepted 8/26/80.

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