Plasma membrane-resident glucocorticoid receptors in rodent lymphoma and human leukemia models

Bahiru Gametchu, Fanghong Chen, Faustina Sackey, Charles Powell, Cheryl S. Watson

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

The presence of the glucocorticoid (GC) receptor is required for GC- evoked apoptosis. However, the explicit mechanism of involvement of this receptor continues to be debated. Employing the murine (S-49) and human (CCRF-CEM) lymphoid cell lines, we demonstrated that this response requires a specialized form of the glucocorticoid receptor (GR) that resides in the plasma membrane (mGR). Our studies of mGR have been done in our stable mGR- enriched (by sequential cell separation - immunopanning, fluorescent cell sorting, soft agar cloning) S-49 and CCRF-CEM cells. Direct and indirect immunofluorescent studies of live intact cells showed GR-specific periplasma membrane staining. Immunoanalysis by flow cytometry demonstrated abundant mGR in mGR++ cells, but only barely detectable mGR in mGR-- cells. Western blot and autoradiographic analyses of immunoprecipitated membrane extracts from these cells show they contain immunoreactive and competitively labeled high M(r) receptor ranging from 94 to 150 kDa. Using mGR++ CCRF-CEM cells and three synchronization procedures (double thymidine, thymidine/colcemid, and colcemid blocks), we have investigated the influence of cell cycle on regulation and function of mGR. Both mGR expression and GC-mediated lymphocytolysis appear highest at late S-G2/M. Analysis of mGR in lymphocytes of several leukemic patients indicated differences in the levels of receptor expression. These findings might provide diagnostic clues about patients' differential response to steroid therapy and potential therapeutic avenues for effective treatment of hormone-responsive leukemic patients.

Original languageEnglish (US)
Pages (from-to)107-119
Number of pages13
JournalSteroids
Volume64
Issue number1-2
DOIs
StatePublished - Jan 1 1999

Keywords

  • Acute lymphocytic leukemia (ALL)
  • Cell cycle
  • GR 1A
  • Lymphocytolysis
  • Membrane glucocorticoid receptor
  • Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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