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

Setsuko K. Chambers, Christina M. Ivins, Barry M. Kacinski, Richard B. Hochberg, Michele Follen

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)974-982
Number of pages9
JournalAmerican journal of obstetrics and gynecology
Volume190
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

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Keywords

  • C-fms Proto-oncogene
  • Choriocarcinoma
  • Glucocorticoid
  • Glucocorticoid receptor

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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