Glucocorticoid regulation of parathyroid hormone-related peptide gene transcription in a human neuroendocrine cell line.
A PTH-related peptide (PTHRP) has been identified and its cDNA cloned from tumors associated with the syndrome of humoral hypercalcemia of malignancy. The PTHRP and PTH genes appear to represent members of a gene family. Whereas the PTH gene is expressed exclusively in the parathyroids, the PTHRP gene appears to be widely expressed, but little is known concerning the regulation of its expression in any site. We studied the regulation of PTHRP gene expression in a human carcinoid cell line (NCI-H727) which has neuroendocrine features and also produces calcitonin, calcitonin gene-related peptide, and chromogranin-A. We found that the synthetic glucocorticoid triamcinolone produced time- and dose-dependent decreases in steady state PTHRP and calcitonin mRNA levels in NCI-H727 cells. This effect was blocked by the competitive glucocorticoid inhibitor RU-486. Messenger RNA stability and transcription run-off experiments revealed that triamcinolone decreased PTHRP and calcitonin expression by repressing the transcription rates of both genes.
Lu
C
C
Department of Internal Medicine, Yale University, New Haven, Connecticutt 06511.
Ikeda
K
K
Deftos
L J
LJ
Gazdar
A F
AF
Mangin
M
M
Broadus
A E
AE
D002116:Calcitonin / Q000235:genetics; D002276:Carcinoid Tumor / Q000235:genetics; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D005810:Multigene Family / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000235:genetics; D009490:Neurosecretory Systems; D010281:Parathyroid Hormone / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic; D014221:Triamcinolone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D014221:Triamcinolone; D015735:Mifepristone; D002116:Calcitonin