Patterns of human chorionic gonadotropin expression in untreated and 8-bromoadenosine-treated JAR choriocarcinoma cells.
Although the biosynthesis and secretion of hCG by both normal and neoplastic trophoblasts have been documented, the regulation of these events is not well understood. We have used the JAR choriocarcinoma cell line to study the biosynthesis and secretion of this hormone. Using immunofluorescence, we have determined that less than 5% of cells expressed detectable hCG at a given time, and about 30% of hCG-producing cells were morphologically differentiated. Treatment of the cells with 8-bromoadenosine produced a 2- to 5-fold increase in hCG synthesis and secretion and increased the number of cells expressing hCG by 4- to 6-fold, without altering the percentage of morphologically differentiated cells expressing hCG. The effect on hCG biosynthesis was dose dependent and was induced maximally with a 24-h exposure to 8-bromoadenosine. However, exposure of JAR cells to 8-bromoadenosine for 2 to 6 h was sufficient to initiate a response. Treatment of JAR cells with the adenosine A2-receptor agonist N-ethylcarboxamidoadenosine did not induce hCG biosynthesis. The effect of 8-bromoadenosine on hCG synthesis did, however, parallel the dose-effect curve for inhibition of thymidine incorporation and for decreased cell proliferation. We conclude that induction of hCG biosynthesis by 8-bromoadenosine occurs by inhibiting trophoblast cell proliferation, rather than by an adenosine receptor-mediated event. The observed increase in hCG production may be due to induction of an intermediate differentiated cell type or an increase in the number of cells in an hCG-producing cell cycle phase.
Martell
R E
RE
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Ruddon
R W
RW
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007163:Immunosorbent Techniques; D007700:Kinetics; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D011983:Receptors, Purinergic; C036038:8-bromoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine