Expression and cAMP-mediated regulation of the human gonadotropin alpha subunit gene in transfected mouse L-cells

Abstract

Abstract Expression of the dimeric glycoprotein hormone, human chorionic gonadotropin (HCG), occurs either eutopically in placental trophoblast cells and trophoblastic tumor cells (choriocarcinoma) or ectopically in nontrophoblastic tumor cells. However, regulation of constitutive HCG-subunit mRNA production appears to differ in trophoblastic and nontrophoblastic cells, as evidenced by the fact that cAMP analogs and agonists enhance cutopic but not ectopic HCG-subunit mRNA synthesis. In the present study, we compared the effects of cAMP on HCG α-subunit expression in human choriocarcinoma cells and in nontrophoblastic mouse L-cells stably transfected with the HCG α-subunit gene. Constitutive levels of α-subunit expression in transfected mouse L-cells were equivalent to or exceeded those found in choriocarcinoma cells as determined by Northern blot analysis and indirect immunofluorescence for α-subunit protein. However, cAMP-mediated induction of α-subunit gene expression was retained in nontrophoblastic L-cells and closely paralleled that observed in human choriocarcinoma cells. These findings indicate that cells distinctly nontrophoblastic in origin may share the necessary cellular factors for cAMP-mediated induction of α-subunit gene expression. Failure of ectopic HCG-producing tumor cells to be stimulated by cAMP may thus be the result of deletion or mutation of such factors.