Alimentary TractOncogenic ras induces gastrin gene expression in colon cancer☆,☆☆
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Cell lines and tissues
All cell lines were obtained from the American Type Culture Collection (Manassas, VA). Cells were cultured in the following media: RPMI 1640 (Colo320HSR and Colo205), Dulbecco's modified Eagle medium with high glucose (HT29, Hct116, Caco-2, and LoVo), and Leibovitz's L-15 (SW480), each supplemented with 10% fetal bovine serum (BioWhittaker, Walkersville, MD) and 2% penicillin/streptomycin (10,000 U/mL). Surgical specimens were snap-frozen on resection and stored at −80°C. Treatment of cells
Gastrin mRNA levels in colon cancer
A sensitive RPA was developed for the detection and quantification of gastrin mRNA levels in colon cancer cell lines and tissue samples obtained from surgical resection. Antisense riboprobes derived from human gastrin (exon 2) and cyclophilin gene templates were used in each assay. Cyclophilin mRNA, transcribed from a ubiquitous housekeeping gene, served as an internal control for mRNA integrity and reaction conditions. Total RNA samples from seven colon cancer cell lines and two pairs of human
Discussion
Several studies have noted that colon cancer tumors often have increased levels of gastrin peptides, particularly incompletely processed forms.14, 15, 18 Normal gastrin expression in the colon appears to be much higher during fetal development than after maturity.17 Hence, the elevated expression of gastrin in colon cancer likely occurs through oncofetal transcriptional mechanisms, which to date have not been well characterized. The results of this study establish that oncogenic activation of
Acknowledgements
The authors thank Drs. Channing Der (kinase expression vectors and p(Py)2Luc), Richard Rippe (pGL Col3 Luc), and Timothy Wang (pGem gastrin exon 2) for providing plasmids; Drs. David Brenner, Cyndi Bradham, Laura Licato, and Martin McMahon for helpful discussions; Dr. Shrikant Bangdiwala for advice about statistical analysis; and Dr. Kevin Behrns (University of North Carolina) and Tissue Procurement facilities at the Lineberger Cancer Center (University of North Carolina) and Massachusetts
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Gastrin mediates resistance to hypoxia-induced cell death in xenografts of the human colorectal cancer cell line LoVo
2014, Biochimica et Biophysica Acta - Molecular Cell ResearchIdentification of the F<inf>1</inf>-ATPase at the cell surface of colonic epithelial cells: Role in mediating cell proliferation
2012, Journal of Biological ChemistryCitation Excerpt :It is, therefore, interesting to notice that the new ligand of F1-ATPase that we have identified in the present study is also overexpressed in these tumor cells. Indeed, the gene coding for gastrin is a target of oncogenic pathways frequently activated in colon cancer such as APC/β-catenin or Ras pathways (38–41). Therefore, high concentrations of gastrin precursors, including G-gly have been observed in colon tumors and in blood of patients with colorectal cancer (42–45).
No higher risk for colorectal cancer in atrophic gastritis-related hypergastrinemia
2012, Digestive and Liver DiseaseGastrointestinal Peptides: Gastrin, Cholecystokinin, Somatostatin, and Ghrelin. Gastrin, Cholecystokinin, Somatostatin, and Ghrelin
2012, Physiology of the Gastrointestinal Tract, Two Volume Set
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Address requests for reprints to: Loyal G. Tillotson, M.D., Ph.D., CB 7038, Room 148, Glaxo Building, University of North Carolina, Chapel Hill, North Carolina 27599-7038, e-mail: [email protected]; fax: (919) 966- 7468.
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Supported by grant R29 DK49860 from the National Institutes of Health, a grant from the Glaxo Institute of Digestive Health Basic Research, and grant P30DK34987 from the Center for Gastrointestinal Biology and Disease.