The intestinal nuclear receptor signature with epithelial localization patterns and expression modulation in tumors.
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.
Modica
Salvatore
S
Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
Gofflot
Francoise
F
Murzilli
Stefania
S
D'Orazio
Andria
A
Salvatore
Lorena
L
Pellegrini
Fabio
F
Nicolucci
Antonio
A
Tognoni
Giovanni
G
Copetti
Massimiliano
M
Valanzano
Rosa
R
Veschi
Serena
S
Mariani-Costantini
Renato
R
Palasciano
Giuseppe
G
Schoonjans
Kristina
K
Auwerx
Johan
J
Moschetta
Antonio
A
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
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear