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

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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
Pages (from-to)180-186
Number of pages7
Issue number2
StatePublished - Aug 1997

Bibliographical note

Funding Information:
Supported by grants from the National Institutes of Health (ROl DK48498, ROl AG10885, PO1 DK35608, T32 DK07639), the UTMB Jeane B. Kempner Scholar Award Fund, and the James E. Thompson Memorial Foundation. Presented at the Fifty-eighth Annual Meeting of the Society of University Surgeons, Tampa, Fla., Feb. 13-15, 1997. Reprint requests: B. Mark Evers, MD, Department of Surgery, The University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0533. Copyright 0 1997 by Mosby-Year Book, Inc. 0039-6060/97/$5.00 + 0 11/6/81922

ASJC Scopus subject areas

  • Surgery


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