Dexamethasone regulation of gastrin-releasing peptide receptor in human lung cells.
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 12h of 10nM 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/microg total RNA, respectively, P<0.05) occurred. GRP receptor mRNA levels fell to less than 0.5 attomols/microg total RNA after 24h; in Dex-treated cells, these levels rose to 1.2 compared with 0.12 attomols/microg 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.
Novak
John
J
Section of Medical Oncology, Denver Veterans Affairs Medical Center, University of Colorado Health Sciences Center and University of Colorado Cancer Center, 1055 Clermont Street, Denver, CO 80220, USA.
Schleman
Shea
S
Scott
Jennifer
J
Balderman
Valerie L
VL
Krech
Laura
L
Kane
Madeleine A
MA
D002455:Cell Division / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D019886:Gastrin-Releasing Peptide / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018004:Receptors, Bombesin; D003907:Dexamethasone; D019886:Gastrin-Releasing Peptide