TY - JOUR
T1 - The Intestinal Nuclear Receptor Signature With Epithelial Localization Patterns and Expression Modulation in Tumors
AU - Modica, Salvatore
AU - Gofflot, Francoise
AU - Murzilli, Stefania
AU - D'Orazio, Andria
AU - Salvatore, Lorena
AU - Pellegrini, Fabio
AU - Nicolucci, Antonio
AU - Tognoni, Giovanni
AU - Copetti, Massimiliano
AU - Valanzano, Rosa
AU - Veschi, Serena
AU - Mariani-Costantini, Renato
AU - Palasciano, Giuseppe
AU - Schoonjans, Kristina
AU - Auwerx, Johan
AU - Moschetta, Antonio
N1 - Funding Information:
Funding This work was funded by the Italian Association for Cancer Research (Start-Up grant 2005, AIRC, Milan, Italy), University of Bari (ORBA07X7Q1 and ORBA06BXVC, Bari, Italy), CARISPAQ (L'Aquila, Italy), ERC-STG-FIRB-IDEAS (RBID08C9N7), INSERM, CNRS, Université Louis Pasteur (Strasbourg, France), and EPFL (Lausanne, Switzerland).
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2010/2
Y1 - 2010/2
N2 - Background & Aims: The WNT-adenomatous polyposis coli system controls cell fate in the intestinal epithelium, where compartment-specific genes tightly regulate proliferation, migration, and differentiation. Nuclear receptors are transcription factors functioning as sensors of hormones and nutrients that are known to contribute to colon cancer progression. Here we mapped the messenger RNA (mRNA) abundance and the epithelial localization of the entire nuclear receptor family in mouse and human intestine. Methods: We used complementary high-resolution in situ hybridization and systematic real-time quantitative polymerase chain reaction in samples of normal distal ileum and proximal colon mucosa and tumors obtained from mouse and human adenomatous polyposis coli-initiated tumor models (ie, ApcMin/+ mice and familial adenomatous polyposis patients) and in cellular models of human colon cancer. Results: We first defined for each receptor an expression pattern based on its transcript localization in the distal ileum and the proximal colon. Then, we compared the mRNA levels between normal intestinal epithelium and neoplastic intestinal tissue. After analyzing the correspondence between mouse and human tumor samples plus genetically modified human colon cancer cells, we used complementary graphic and statistical approaches to present a comprehensive overview with several classification trees for the nuclear hormone receptor intestinal transcriptome. Conclusions: We defined the intestinal nuclear hormone receptor map, which indicates that the localization pattern of a receptor in normal intestine predicts the modulation of its expression in tumors. Our results are useful to select those nuclear receptors that could be used eventually as early diagnostic markers or targeted for clinical intervention in intestinal polyposis and cancer.
AB - Background & Aims: The WNT-adenomatous polyposis coli system controls cell fate in the intestinal epithelium, where compartment-specific genes tightly regulate proliferation, migration, and differentiation. Nuclear receptors are transcription factors functioning as sensors of hormones and nutrients that are known to contribute to colon cancer progression. Here we mapped the messenger RNA (mRNA) abundance and the epithelial localization of the entire nuclear receptor family in mouse and human intestine. Methods: We used complementary high-resolution in situ hybridization and systematic real-time quantitative polymerase chain reaction in samples of normal distal ileum and proximal colon mucosa and tumors obtained from mouse and human adenomatous polyposis coli-initiated tumor models (ie, ApcMin/+ mice and familial adenomatous polyposis patients) and in cellular models of human colon cancer. Results: We first defined for each receptor an expression pattern based on its transcript localization in the distal ileum and the proximal colon. Then, we compared the mRNA levels between normal intestinal epithelium and neoplastic intestinal tissue. After analyzing the correspondence between mouse and human tumor samples plus genetically modified human colon cancer cells, we used complementary graphic and statistical approaches to present a comprehensive overview with several classification trees for the nuclear hormone receptor intestinal transcriptome. Conclusions: We defined the intestinal nuclear hormone receptor map, which indicates that the localization pattern of a receptor in normal intestine predicts the modulation of its expression in tumors. Our results are useful to select those nuclear receptors that could be used eventually as early diagnostic markers or targeted for clinical intervention in intestinal polyposis and cancer.
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U2 - 10.1053/j.gastro.2009.09.060
DO - 10.1053/j.gastro.2009.09.060
M3 - Article
C2 - 19818784
AN - SCOPUS:75449115416
SN - 0016-5085
VL - 138
SP - 636-648.e12
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -