Src-mediated activation of the human neurotensin/neuromedin N promoter

Nitesh A. Banker, Mark Hellmich, Hong Jin Kim, Courtney Townsend, B. Mark Evers

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)180-186
Number of pages7
JournalSurgery
Volume122
Issue number2
DOIs
StatePublished - Aug 1997

Fingerprint

neuromedin N
Neurotensin
Caco-2 Cells
Luciferases
Plasmids
Galactosidases
Gene Expression
src-Family Kinases
Transcription Factor AP-1
Cyclic AMP
Protein-Tyrosine Kinases
Colonic Neoplasms

ASJC Scopus subject areas

  • Surgery

Cite this

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 journalArticle

Banker, Nitesh A. ; Hellmich, Mark ; Kim, Hong Jin ; Townsend, Courtney ; Evers, B. Mark. / Src-mediated activation of the human neurotensin/neuromedin N promoter. In: Surgery. 1997 ; Vol. 122, No. 2. pp. 180-186.
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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.",
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