The Intestinal Nuclear Receptor Signature With Epithelial Localization Patterns and Expression Modulation in Tumors

Salvatore Modica, Francoise Gofflot, Stefania Murzilli, Andria D'Orazio, Lorena Salvatore, Fabio Pellegrini, Antonio Nicolucci, Giovanni Tognoni, Massimiliano Copetti, Rosa Valanzano, Serena Veschi, Renato Mariani-Costantini, Giuseppe Palasciano, Kristina Schoonjans, Johan Auwerx, Antonio Moschetta

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
JournalGastroenterology
Volume138
Issue number2
DOIs
Publication statusPublished - Feb 2010

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Cytoplasmic and Nuclear Receptors
Adenomatous Polyposis Coli
Colonic Neoplasms
Intestinal Mucosa
Neoplasms
Ileum
Gastrointestinal Hormone Receptors
Intestines
Colon
Intestinal Polyposis
Intestinal Neoplasms
Messenger RNA
Nuclear Family
Transcriptome
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Mucous Membrane
Transcription Factors
Hormones
Food

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Modica, S., Gofflot, F., Murzilli, S., D'Orazio, A., Salvatore, L., Pellegrini, F., ... Moschetta, A. (2010). The Intestinal Nuclear Receptor Signature With Epithelial Localization Patterns and Expression Modulation in Tumors. Gastroenterology, 138(2). https://doi.org/10.1053/j.gastro.2009.09.060

The Intestinal Nuclear Receptor Signature With Epithelial Localization Patterns and Expression Modulation in Tumors. / Modica, Salvatore; Gofflot, Francoise; Murzilli, Stefania; D'Orazio, Andria; Salvatore, Lorena; Pellegrini, Fabio; Nicolucci, Antonio; Tognoni, Giovanni; Copetti, Massimiliano; Valanzano, Rosa; Veschi, Serena; Mariani-Costantini, Renato; Palasciano, Giuseppe; Schoonjans, Kristina; Auwerx, Johan; Moschetta, Antonio.

In: Gastroenterology, Vol. 138, No. 2, 02.2010.

Research output: Contribution to journalArticle

Modica, S, Gofflot, F, Murzilli, S, D'Orazio, A, Salvatore, L, Pellegrini, F, Nicolucci, A, Tognoni, G, Copetti, M, Valanzano, R, Veschi, S, Mariani-Costantini, R, Palasciano, G, Schoonjans, K, Auwerx, J & Moschetta, A 2010, 'The Intestinal Nuclear Receptor Signature With Epithelial Localization Patterns and Expression Modulation in Tumors', Gastroenterology, vol. 138, no. 2. https://doi.org/10.1053/j.gastro.2009.09.060
Modica, Salvatore ; Gofflot, Francoise ; Murzilli, Stefania ; D'Orazio, Andria ; Salvatore, Lorena ; Pellegrini, Fabio ; Nicolucci, Antonio ; Tognoni, Giovanni ; Copetti, Massimiliano ; Valanzano, Rosa ; Veschi, Serena ; Mariani-Costantini, Renato ; Palasciano, Giuseppe ; Schoonjans, Kristina ; Auwerx, Johan ; Moschetta, Antonio. / The Intestinal Nuclear Receptor Signature With Epithelial Localization Patterns and Expression Modulation in Tumors. In: Gastroenterology. 2010 ; Vol. 138, No. 2.
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