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. 1996 Aug;74(3):432–438. doi: 10.1038/bjc.1996.377

Beta-adrenergic signalling in neoplastic lung type 2 cells: glucocorticoid-dependent and -independent defects.

K A Droms 1
PMCID: PMC2074634  PMID: 8695360

Abstract

Tumorigenic mouse lung-derived type 2 cell lines have large reductions in both beta-adrenergic-stimulated cAMP production and ligand binding to beta-adrenergic receptors. These tumorigenic cells are also relatively insensitive to glucocorticoids. Because glucocorticoids regulate both beta-adrenergic receptor expression and receptor coupling to the stimulatory guanine nucleotide binding protein Gs interactions between the glucocorticoid and beta-adrenergic signalling systems were examined. This study demonstrates that beta-adrenergic ligand binding and agonist sensitivity are increased in a tumorigenic cell line stably expressing a normal glucocorticoid receptor transgene. However, although the transfected tumour cells and non-tumorigenic cells have similar amounts and affinities of beta-adrenergic agonist and antagonist binding, similar amounts of Gs subunits and similar forskolin-stimulated adenylyl cyclase activities, the former remain much less isoproterenol responsive. Competition binding studies demonstrate that tumour cell beta-adrenergic receptors have both high- and low-affinity agonist binding but are functionally uncoupled from Gs. This uncoupling may involve an alteration in Gs, as guanine nucleotides exhibit a reduced ability to stimulate adenylyl cyclase. Thus, some aspects of tumorigenic cell dysfunction in beta-adrenergic signalling can be ameliorated by interactions with the glucocorticoid pathway, but additional defects are also involved.

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Selected References

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