title: The intestinal nuclear receptor signature with epithelial localization patterns and expression modulation in tumors.
abstract: OBJECTIVE
  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, Apc(Min/+) 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.
authors.affiliation: Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Modica
authors.forename: Francoise
authors.initials: F
authors.lastname: Gofflot
authors.forename: Stefania
authors.initials: S
authors.lastname: Murzilli
authors.forename: Andria
authors.initials: A
authors.lastname: D'Orazio
authors.forename: Lorena
authors.initials: L
authors.lastname: Salvatore
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Antonio
authors.initials: A
authors.lastname: Nicolucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tognoni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Rosa
authors.initials: R
authors.lastname: Valanzano
authors.forename: Serena
authors.initials: S
authors.lastname: Veschi
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palasciano
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Antonio
authors.initials: A
authors.lastname: Moschetta
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000818:Animals; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear