TY - JOUR
T1 - Expression of neurotensin messenger RNA in a human carcinoid tumor
AU - Evers, B. M.
AU - Ishizuka, J.
AU - Townsend, C. M.
AU - Rajaraman, S.
AU - Thompson, J. C.
PY - 1991/10
Y1 - 1991/10
N2 - Neurotensin (NT), a distal gut peptide, has important regulatory and trophic effects throughout the gut; however the intracellular mechanisms that regulate the gene expression and release of human NT are not known. The purpose of this endeavor was to study a functioning human pancreatic carcinoid cell line (called BON) in vitro that expresses the NT gene, and to study the effect of the cyclic adenosine monophosphate (cAMP) signal-transduction pathway on the expression and release of human NT. RNA was prepared from BON cell line (which has been established in this laboratory); the RNA was analyzed for NT mRNA expression by Northern hybridization with a complementary DNA probe. RNA blot analysis demonstrated that the NT gene is expressed in BON and is transcribed to two mRNAs of 1.0- and 1.5-kb sizes. In the second part of this study, BON cells were treated with either forskolin (FSK), which increases intracellular levels of cAMP, or with serotonin (S-HT), which reduces cAMP in BON cells. Forskolin produced a dose-dependent increase in NT peptide release and, furthermore, FSK (10-6 mol/L) rapidly increased NT mRNA abundance 1 hour after addition; conversely, 5-HT (10-5 mol/L) decreased NT mRNA at 1 hour. Neurotensin mRNA levels returned to control values by 3 hours after either FSK or 5-HT, which suggests that the transcript half-life for NT is relatively short. These findings show that the expression and peptide release of human NT is mediated, in part, by the cAMP signal-transduction pathway. Our human carcinoid cell line will provide a useful model to study the in vitro regulation of NT gene expression and peptide release.
AB - Neurotensin (NT), a distal gut peptide, has important regulatory and trophic effects throughout the gut; however the intracellular mechanisms that regulate the gene expression and release of human NT are not known. The purpose of this endeavor was to study a functioning human pancreatic carcinoid cell line (called BON) in vitro that expresses the NT gene, and to study the effect of the cyclic adenosine monophosphate (cAMP) signal-transduction pathway on the expression and release of human NT. RNA was prepared from BON cell line (which has been established in this laboratory); the RNA was analyzed for NT mRNA expression by Northern hybridization with a complementary DNA probe. RNA blot analysis demonstrated that the NT gene is expressed in BON and is transcribed to two mRNAs of 1.0- and 1.5-kb sizes. In the second part of this study, BON cells were treated with either forskolin (FSK), which increases intracellular levels of cAMP, or with serotonin (S-HT), which reduces cAMP in BON cells. Forskolin produced a dose-dependent increase in NT peptide release and, furthermore, FSK (10-6 mol/L) rapidly increased NT mRNA abundance 1 hour after addition; conversely, 5-HT (10-5 mol/L) decreased NT mRNA at 1 hour. Neurotensin mRNA levels returned to control values by 3 hours after either FSK or 5-HT, which suggests that the transcript half-life for NT is relatively short. These findings show that the expression and peptide release of human NT is mediated, in part, by the cAMP signal-transduction pathway. Our human carcinoid cell line will provide a useful model to study the in vitro regulation of NT gene expression and peptide release.
UR - http://www.scopus.com/inward/record.url?scp=0025997673&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025997673&partnerID=8YFLogxK
M3 - Article
C2 - 1659338
AN - SCOPUS:0025997673
SN - 0003-4932
VL - 214
SP - 448
EP - 454
JO - Annals of Surgery
JF - Annals of Surgery
IS - 4
ER -