Expression and secretion of parathyroid hormone-related protein by a human cancer cell line.
The regulation of expression of parathyroid hormone-related protein (PTHRP) mRNA by protein kinase C and cyclic-AMP-dependent pathways was studied in a human lung cancer cell line (BEN). PTHRP mRNA was increased by agents which activate protein kinase C, but not by those which activate cyclic-AMP-dependent pathways. Activators of both second messenger pathways stimulated a dose-dependent increase in the accumulation of PTHRP in conditioned medium assayed using sensitive region-specific immunoassays for PTHRP1-34 and 1-86. Calcitonin had a dose-dependent effect on the accumulation of PTHRP in culture medium which may be mediated via cyclic AMP. Varying the calcium concentration from 0-2.5 mM had no effect on peptide secretion over 20 h, while short-term incubation (30 min) with ionomycin (2.5-75 micrograms/ml) significantly increased PTHRP immunoreactivity in the medium.
Emly
J F
JF
Wolfson Research Laboratories, Department of Clinical Chemistry, Queen Elizabeth Medical Centre, Edgbaston, Birmingham, UK.
Hughes
S
S
Green
E
E
Ratcliffe
W A
WA
D002116:Calcitonin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007118:Immunoassay; D044162:Parathyroid Hormone-Related Protein; D010703:Phorbol Esters / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010703:Phorbol Esters; D011506:Proteins; D012333:RNA, Messenger; D003609:Dactinomycin; D002116:Calcitonin; D003513:Cycloheximide; D000242:Cyclic AMP