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American Journal of Respiratory Cell and Molecular Biology. Vol. 27, pp. 361-367, 2002
© 2002 American Thoracic Society
DOI: 10.1165/rcmb.4861

Increased Glucocorticoid Receptor ß Expression Converts Mouse Hybridoma Cells to a Corticosteroid-Insensitive Phenotype

Pia J. Hauk, Elena Goleva, Ian Strickland, Alessandra Vottero, George P. Chrousos, Kevin O. Kisich and Donald Y. M. Leung

Department of Pediatrics, National Jewish Medical and Research Center, Denver; Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; and Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Development, National Institutes of Health, Bethesda, Maryland

Address correspondence to: Donald Y. M. Leung, M.D., Ph.D., National Jewish Medical Research Center, 1400 Jackson Street, Room K926i, Denver, CO 80206. E-mail: leungd{at}njc.org

Glucocorticoid (GC) insensitivity is a challenging clinical problem associated with many chronic inflammatory disorders and life-threatening disease progression. The molecular basis of GC insensitivity, however, is unknown. Alternative splicing of the GC receptor (GCR) pre-mRNA generates a second GCR, termed GCRß, which does not bind GC but antagonizes the transactivating activity of the classic GCR, termed GCR{alpha}. GC-insensitive conditions have been associated with increased GCRß expression. Whether or not increased GCRß expression can contribute to GC insensitivity, however, remains controversial. To more precisely demonstrate the effect of GCRß on steroid responsiveness, we virally transduced GCRß cDNA into mouse DO-11.10 hybridoma cells, as mice are known to be deficient in the GCRß gene. We demonstrate that viral transduction of GCRß cDNA into mouse hybridoma cells to induce stable expression of GCRß results in GC insensitivity of these cells. Furthermore, in such cells GCR{alpha} is complexed with GCRß. Such heterodimer formation may account for the reduced effectiveness of GC action in cells overexpressing GCRß.

Abbreviations: bovine serum albumin, BSA • dexamethasone, DEX • fetal calf serum, FCS • glucocorticoid, GC • glucocorticoid receptor, GCR • green fluorescent protein, GFP • glucocorticoid-responsive element, GRE • human glucocorticoid receptor ß, hGCRß • Iscove's modified Dulbecco's medium, IMDM • mouse mammary tumor virus, MMTV • murine stem cell virus, MSCV • peripheral blood mononuclear cells, PBMC




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