An unexpected effect of glucocorticoids on stimulation of c-fms proto-oncogene expression in choriocarcinoma cells that express little glucocorticoid receptor

Objective The purpose of this study was to determine the mechanism by which glucocorticoids stimulate c-fms proto-oncogene expression in JAR choriocarcinoma cells, which are reported to lack the glucocorticoid receptor. Study design Glucocorticoid action on c-fms was tested with the use of ligand binding assays, Northern and Western blotting, immunohistochemistry, quantitative reverse transcriptase–polymerase chain reaction, and nuclear run-off experiments. Results Dexamethasone stimulated c-fms (EC50=1 nmol/L) in JAR cells in a specific manner. Both RU 486 and actinomycin D inhibited dexamethasone stimulation, which suggests receptor-mediated and transcriptionally regulated actions. Neither cytosol or whole cell binding assays nor immunohistochemistry detected glucocorticoid receptor in JAR cells. However, Southern blot analysis of reverse transcriptase–polymerase chain reaction products revealed levels of glucocorticoid receptor messenger RNA in JAR cells that were approximately 100-fold lower than in HeLa control cells. In all but 1 clone among several JAR clones that were tested, there was concordance between presence or absence of glucocorticoid receptor messenger RNA and glucocorticoid sensitivity. Conclusion Some JAR cells contain low levels of glucocorticoid receptor, which mediate dexamethasone stimulation of c-fms expression. Such sensitivity to circulating glucocorticoids confers a survival advantage to these cells by stimulating the c-fms–related invasive behavior so characteristic of choriocarcinomas.