Fetal and Neoplastic Expression of the Neurotensin Gene in the Human Colon

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Abstract
Objective The authors identified various colon cancers that express the gene for the gut peptide neurotensin (NT/N). In addition, the authors sought to delineate the temporal pattern of NT/N gene expression in the human fetal colon. Summary Background Data Expression of NT/N is localized to the mucosa of the adult small bowel but also has been identified in the fetal colon, which resembles the small bowel until the end of the second trimester. Ectopic NT/N expression has been shown in certain types of colon cancer, suggesting a reversion to a fetal phenotype. Methods Sensitive ribonuclease protection assays were used to determine NT/N expression in colon cancers and adjacent normal mucosa as well as colon cancers established as tumor xenografts and fetal colon samples. Results NT/N gene expression was shown in 4 of 12 (25%) human colon cancer xenografts and in 11 of 40 (28%) freshly resected colon adenocarcinomas; NT/N gene expression was not expressed in any of the samples of normal colonic mucosa adjacent to the tumors. The NT/N gene was expressed maximally in the fetal colon between 16 and 18 weeks' gestation; NT/N expression was decreased between 19 and 22 weeks and was not apparent in either the 24-week fetal colon or the adult samples. Conclusions The NT/N gene expression is expressed transiently in the fetal colon during a development stage that is characterized by morphologic similarity to the small bowel. In addition, NT/N is re-expressed in approximately one fourth of the human colon cancers, indicating that neoplastic transformation leads to reversion to a fetal phenotype in certain types of colon cancer. The NT/N gene will provide a useful model to further define the complex differentiation pathways in the normal gut as well as the process of fetal “dedifferentiation” in certain types of colon cancer.