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 Citations (Scopus)

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 (EC 50 = 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)974-985
Number of pages12
JournalAmerican Journal of Obstetrics and Gynecology
Volume190
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

fms Genes
Choriocarcinoma
Glucocorticoid Receptors
Glucocorticoids
Dexamethasone
Reverse Transcriptase Polymerase Chain Reaction
Clone Cells
Immunohistochemistry
Mifepristone
Messenger RNA
Dactinomycin
Southern Blotting
HeLa Cells
Northern Blotting
Cytosol
Western Blotting
Ligands

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

An unexpected effect of glucocorticoids on stimulation of c-fms proto-oncogene expression in choriocarcinoma cells that express little glucocorticoid receptor. / Chambers, Setsuko K; Ivins, Christina M.; Kacinski, Barry M.; Hochberg, Richard B.; Follen, Michele.

In: American Journal of Obstetrics and Gynecology, Vol. 190, No. 4, 04.2004, p. 974-985.

Research output: Contribution to journalArticle

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