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Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an early event in human colonic adenomas.
Carcinogenesis. 2006 Apr; 27(4):708-16.C

Abstract

Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway, resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene activation, are frequently detected in familial and sporadic colon cancers. The neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal tract. Its proliferative and survival effects are mediated by a G-protein coupled receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon epithelial cells, but is over expressed in a number of cancer cells and tissues suggesting a link to the outgrowth of human colon cancer. Our results demonstrate that the upregulation of NT1 receptor occurring in colon cancer is the result of Wnt/APC signalling pathway activation. We first established the functionality of the Tcf response element within the NT1 receptor promoter. Consequently, we observed the activation of NT1 receptor gene by agents causing beta-catenin cytosolic accumulation, as well as a strong decline of endogenous receptor when wt-APC was restored. At the cellular level, the re-establishment of wt-APC phenotype resulted in the impaired functionality of NT1 receptor, like the breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro-invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1 receptor promoter activation with human colon carcinogenesis, and showed that NT1 receptor gene activation was perfectly correlated with nuclear or cytoplasmic beta-catenin localization while NT1 receptor was absent when beta-catenin was localized at the cell-cell junction in early adenomas of patients with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of heterozygosity tumours. In this report we establish a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation.

Authors+Show Affiliations

INSERM U673-UPMC, Department of Pathology, 184 Rue Du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16299383

Citation

Souazé, Frédérique, et al. "Neurotensin Receptor 1 Gene Activation By the Tcf/beta-catenin Pathway Is an Early Event in Human Colonic Adenomas." Carcinogenesis, vol. 27, no. 4, 2006, pp. 708-16.
Souazé F, Viardot-Foucault V, Roullet N, et al. Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an early event in human colonic adenomas. Carcinogenesis. 2006;27(4):708-16.
Souazé, F., Viardot-Foucault, V., Roullet, N., Toy-Miou-Leong, M., Gompel, A., Bruyneel, E., Comperat, E., Faux, M. C., Mareel, M., Rostène, W., Fléjou, J. F., Gespach, C., & Forgez, P. (2006). Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an early event in human colonic adenomas. Carcinogenesis, 27(4), 708-16.
Souazé F, et al. Neurotensin Receptor 1 Gene Activation By the Tcf/beta-catenin Pathway Is an Early Event in Human Colonic Adenomas. Carcinogenesis. 2006;27(4):708-16. PubMed PMID: 16299383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an early event in human colonic adenomas. AU - Souazé,Frédérique, AU - Viardot-Foucault,Véronique, AU - Roullet,Nicolas, AU - Toy-Miou-Leong,Mireille, AU - Gompel,Anne, AU - Bruyneel,Erik, AU - Comperat,Eva, AU - Faux,Maree C, AU - Mareel,Marc, AU - Rostène,William, AU - Fléjou,Jean-François, AU - Gespach,Christian, AU - Forgez,Patricia, Y1 - 2005/11/19/ PY - 2005/11/22/pubmed PY - 2006/5/4/medline PY - 2005/11/22/entrez SP - 708 EP - 16 JF - Carcinogenesis JO - Carcinogenesis VL - 27 IS - 4 N2 - Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway, resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene activation, are frequently detected in familial and sporadic colon cancers. The neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal tract. Its proliferative and survival effects are mediated by a G-protein coupled receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon epithelial cells, but is over expressed in a number of cancer cells and tissues suggesting a link to the outgrowth of human colon cancer. Our results demonstrate that the upregulation of NT1 receptor occurring in colon cancer is the result of Wnt/APC signalling pathway activation. We first established the functionality of the Tcf response element within the NT1 receptor promoter. Consequently, we observed the activation of NT1 receptor gene by agents causing beta-catenin cytosolic accumulation, as well as a strong decline of endogenous receptor when wt-APC was restored. At the cellular level, the re-establishment of wt-APC phenotype resulted in the impaired functionality of NT1 receptor, like the breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro-invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1 receptor promoter activation with human colon carcinogenesis, and showed that NT1 receptor gene activation was perfectly correlated with nuclear or cytoplasmic beta-catenin localization while NT1 receptor was absent when beta-catenin was localized at the cell-cell junction in early adenomas of patients with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of heterozygosity tumours. In this report we establish a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/16299383/Neurotensin_receptor_1_gene_activation_by_the_Tcf/beta_catenin_pathway_is_an_early_event_in_human_colonic_adenomas_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgi269 DB - PRIME DP - Unbound Medicine ER -