Dexamethasone regulation of gastrin-releasing peptide receptor in human lung cells

Abstract

We investigated the effects of the glucocorticoid, dexamethasone (Dex), on expression of the gastrin-releasing peptide (GRP) receptor by human small cell lung carcinoma (SCLC) SHP77 cells. After 12 h of 10 nM Dex exposure, a six-fold increase in the peak of GRP receptor mRNA compared with untreated controls (10.5±4 versus 1.65±0.15 attomols/μg total RNA, respectively, P<0.05) occurred. GRP receptor mRNA levels fell to less than 0.5 attomols/μg total RNA after 24 h; in Dex-treated cells, these levels rose to 1.2 compared with 0.12 attomols/μg total RNA in the absence of Dex after 7 days. A significant increase ( P<0.05) in the GRP receptor-specific binding was also found. Stimulation of SHP77 cell proliferation (25–35% in the presence of 10–100 nM Dex; P<0.0001) was observed after 4–8 days of exposure; this stimulation was inhibited by GRP receptor antagonists. SHP77 cell content and concentration of bombesin-like peptides (BLP) in conditioned medium (approximately 4 nM) was unchanged by Dex. Stimulation of human SCLC SHP77 cell proliferation by Dex may, in part, occur via effects on the GRP autocrine system in these cells.