Abstract
Background. Expression of the gene encoding the neurotensin/neuromedin N (NT/N) is developmentally regulated in the gut in a distinctive temporal and spatial fashion. Src kinase, a nonreceptor tyrosine kinase, has been implicated in the growth and differentiation of various tissues; its role in gut differentiation is not known. The purpose of this study was to determine whether the Src signaling pathway plays a role in the activation of the human NT/N promoter. Methods. Caco-2 cells, a human colon cancer cell line that can differentiate to a small bowel phenotype, were transiently transfected with human NT/N promoter fragments linked to luciferase and various amounts of Src expression plasmids or dominant negative Raft luciferase and β-galactosidase activities were measured after 48 hours. Results. Cotransfection of Src resulted in an approximate eightfold increase of NT/N promoter activity; mutation of a proximal activating protein-1/cyclic adenosine monophosphate responsive element site resulted in a dramatic decrease of Src-mediated NT/N induction. Cotransfection with a dominant negative Raf plasmid partially blocked Src-mediated NT/N activation. Conclusions. Src increases NT/N promoter activity in Caco-2 cells acting, in part, through a proximal AP- 1/CRE promoter element. In addition, Src regulation of the NT/N promoter appears to be mediated through a Raf-dependent pathway. We propose that Src may play a role in tissue-specific gene expression in the gut.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 180-186 |
| Number of pages | 7 |
| Journal | Surgery |
| Volume | 122 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1997 |
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ASJC Scopus subject areas
- Surgery
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Src-mediated activation of the human neurotensin/neuromedin N promoter. / Banker, Nitesh A.; Hellmich, Mark; Kim, Hong Jin; Townsend, Courtney; Evers, B. Mark.
In: Surgery, Vol. 122, No. 2, 08.1997, p. 180-186.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Src-mediated activation of the human neurotensin/neuromedin N promoter
AU - Banker, Nitesh A.
AU - Hellmich, Mark
AU - Kim, Hong Jin
AU - Townsend, Courtney
AU - Evers, B. Mark
PY - 1997/8
Y1 - 1997/8
N2 - Background. Expression of the gene encoding the neurotensin/neuromedin N (NT/N) is developmentally regulated in the gut in a distinctive temporal and spatial fashion. Src kinase, a nonreceptor tyrosine kinase, has been implicated in the growth and differentiation of various tissues; its role in gut differentiation is not known. The purpose of this study was to determine whether the Src signaling pathway plays a role in the activation of the human NT/N promoter. Methods. Caco-2 cells, a human colon cancer cell line that can differentiate to a small bowel phenotype, were transiently transfected with human NT/N promoter fragments linked to luciferase and various amounts of Src expression plasmids or dominant negative Raft luciferase and β-galactosidase activities were measured after 48 hours. Results. Cotransfection of Src resulted in an approximate eightfold increase of NT/N promoter activity; mutation of a proximal activating protein-1/cyclic adenosine monophosphate responsive element site resulted in a dramatic decrease of Src-mediated NT/N induction. Cotransfection with a dominant negative Raf plasmid partially blocked Src-mediated NT/N activation. Conclusions. Src increases NT/N promoter activity in Caco-2 cells acting, in part, through a proximal AP- 1/CRE promoter element. In addition, Src regulation of the NT/N promoter appears to be mediated through a Raf-dependent pathway. We propose that Src may play a role in tissue-specific gene expression in the gut.
AB - Background. Expression of the gene encoding the neurotensin/neuromedin N (NT/N) is developmentally regulated in the gut in a distinctive temporal and spatial fashion. Src kinase, a nonreceptor tyrosine kinase, has been implicated in the growth and differentiation of various tissues; its role in gut differentiation is not known. The purpose of this study was to determine whether the Src signaling pathway plays a role in the activation of the human NT/N promoter. Methods. Caco-2 cells, a human colon cancer cell line that can differentiate to a small bowel phenotype, were transiently transfected with human NT/N promoter fragments linked to luciferase and various amounts of Src expression plasmids or dominant negative Raft luciferase and β-galactosidase activities were measured after 48 hours. Results. Cotransfection of Src resulted in an approximate eightfold increase of NT/N promoter activity; mutation of a proximal activating protein-1/cyclic adenosine monophosphate responsive element site resulted in a dramatic decrease of Src-mediated NT/N induction. Cotransfection with a dominant negative Raf plasmid partially blocked Src-mediated NT/N activation. Conclusions. Src increases NT/N promoter activity in Caco-2 cells acting, in part, through a proximal AP- 1/CRE promoter element. In addition, Src regulation of the NT/N promoter appears to be mediated through a Raf-dependent pathway. We propose that Src may play a role in tissue-specific gene expression in the gut.
UR - http://www.scopus.com/inward/record.url?scp=0030869108&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030869108&partnerID=8YFLogxK
U2 - 10.1016/S0039-6060(97)90007-6
DO - 10.1016/S0039-6060(97)90007-6
M3 - Article
C2 - 9288121
AN - SCOPUS:0030869108
VL - 122
SP - 180
EP - 186
JO - Surgery
JF - Surgery
SN - 0039-6060
IS - 2
ER -