Gastroenterology
Volume 138, Issue 2 , Pages 636-648.e12 , February 2010

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

  • Salvatore Modica

      Affiliations

    • Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • ,
  • Francoise Gofflot

      Affiliations

    • Institut Clinique de la Souris, CNRS/INSERM, Université Louis Pasteur, Illkirch, France
    • ,
  • Stefania Murzilli

      Affiliations

    • Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • ,
  • Andria D'Orazio

      Affiliations

    • Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • ,
  • Lorena Salvatore

      Affiliations

    • Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • ,
  • Fabio Pellegrini

      Affiliations

    • Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • Unit of Biostatistics, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Foggia, Italy
    • ,
  • Antonio Nicolucci

      Affiliations

    • Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • ,
  • Giovanni Tognoni

      Affiliations

    • Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • ,
  • Massimiliano Copetti

      Affiliations

    • Unit of Biostatistics, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Foggia, Italy
    • ,
  • Rosa Valanzano

      Affiliations

    • Department of Clinical Physiopathology, University of Florence, Florence, Italy
    • ,
  • Serena Veschi

      Affiliations

    • Unit of Molecular Pathology and Genomics, Center for Sciences on the Ageing (CeSI), “Gabriele D'Annunzio” University Foundation and Department of Oncology and Neurosciences, Chieti, Italy
    • ,
  • Renato Mariani–Costantini

      Affiliations

    • Unit of Molecular Pathology and Genomics, Center for Sciences on the Ageing (CeSI), “Gabriele D'Annunzio” University Foundation and Department of Oncology and Neurosciences, Chieti, Italy
    • ,
  • Giuseppe Palasciano

      Affiliations

    • Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • ,
  • Kristina Schoonjans

      Affiliations

    • Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    • ,
  • Johan Auwerx

      Affiliations

    • Institut Clinique de la Souris, CNRS/INSERM, Université Louis Pasteur, Illkirch, France
    • Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    • ,
  • Antonio Moschetta

      Affiliations

    • Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy, and Clinica Medica Murri, University of Bari, Bari, Italy
    • Corresponding Author InformationReprint requests Address requests for reprints to: Dr Antonio Moschetta, University of Bari, Consorzio Mario Negri Sud, Via Nazionale 8/A, 66030 Santa Maria Imbaro, Chieti, Italy. fax: (39) 0872-570299

Received 21 January 2009 ,Accepted 29 September 2009.

References 

  1. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127:469–480
  2. van de Wetering M, Sancho E, Verweij C, et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111:241–250
  3. Kinzler KW, Nilbert MC, Su LK, et al. Identification of FAP locus genes from chromosome 5q21. Science. 1991;253:661–665
  4. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–767
  5. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10:789–799
  6. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87:159–170
  7. Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83:835–839
  8. Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995;83:841–850
  9. Francis GA, Fayard E, Picard F, et al. Nuclear receptors and the control of metabolism. Annu Rev Physiol. 2003;65:261–311
  10. McKenna NJ, O'Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell. 2002;108:465–474
  11. Chawla A, Repa JJ, Evans RM, et al. Nuclear receptors and lipid physiology: opening the X-files. Science. 2001;294:1866–1870
  12. D'Errico I, Moschetta A. Nuclear receptors, intestinal architecture and colon cancer: an intriguing link. Cell Mol Life Sci. 2008;65:1523–1543
  13. Mulholland DJ, Dedhar S, Coetzee GA, et al. Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know?. Endocr Rev. 2005;26:898–915
  14. Bookout AL, Jeong Y, Downes M, et al. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006;126:789–799
  15. Yang X, Downes M, Yu RT, et al. Nuclear receptor expression links the circadian clock to metabolism. Cell. 2006;126:801–810
  16. Gofflot F, Chartoire N, Vasseur L, et al. Systematic gene expression mapping clusters nuclear receptors according to their function in the brain. Cell. 2007;131:405–418
  17. Chuang JC, Cha JY, Garmey JC, et al. Nuclear hormone receptor expression in the endocrine pancreas. Mol Endocrinol. 2008;22:2353–2363
  18. Fu M, Sun T, Bookout AL, et al. A nuclear receptor atlas: 3T3-L1 adipogenesis. Mol Endocrinol. 2005;19:2437–2450
  19. Margolis RN, Evans RM, O'Malley BW. The nuclear receptor signaling atlas: development of a functional atlas of nuclear receptors. Mol Endocrinol. 2005;19:2433–2436
  20. Morin PJ, Vogelstein B, Kinzler KW. Apoptosis and APC in colorectal tumorigenesis. Proc Natl Acad Sci U S A. 1996;93:7950–7954
  21. Su LK, Kinzler KW, Vogelstein B, et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 1992;256:668–670
  22. Holm S. A Simple Sequentially Rejective Bonferroni Test Procedure. Scand J Stat. 1979;6:65–70
  23. Liaw A, Wiener M. Classification and regression by random forest. R News. 2002;2:18–22Available from: http://CRAN.R-project.org/doc/Rnews/
  24. Breiman L. Random forests. Machine Learning. 2001;45:5–32
  25. Efron B, Tibshirani RJ. Improvements on cross-validation: the .632+ bootstrap method. J Am Stat Association. 1997;92:548–560
  26. Zhang W, Morris QD, Chang R, et al. The functional landscape of mouse gene expression. J Biol. 2004;3:21
  27. Botrugno OA, Fayard E, Annicotte JS, et al. Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation. Mol Cell. 2004;15:499–509
  28. Schoonjans K, Dubuquoy L, Mebis J, et al. Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation. Proc Natl Acad Sci U S A. 2005;102:2058–2062
  29. Coste A, Dubuquoy L, Barnouin R, et al. LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. Proc Natl Acad Sci U S A. 2007;104:13098–13103
  30. Wada-Hiraike O, Imamov O, Hiraike H, et al. Role of estrogen receptor beta in colonic epithelium. Proc Natl Acad Sci U S A. 2006;103:2959–2964
  31. Modica S, Murzilli S, Salvatore L, et al. Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. Cancer Res. 2008;68:9589–9594
  32. Kallay E, Pietschmann P, Toyokuni S, et al. Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage. Carcinogenesis. 2001;22:1429–1435
  33. Huerta S, Irwin RW, Heber D, et al. 1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) mouse. Cancer Res. 2002;62:741–746
  34. Palmer HG, Gonzalez-Sancho JM, Espada J, et al. Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol. 2001;154:369–387
  35. Saez E, Tontonoz P, Nelson MC, et al. Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nat Med. 1998;4:1058–1061
  36. Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med. 1998;4:1046–1052
  37. Lefebvre AM, Chen I, Desreumaux P, et al. Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat Med. 1998;4:1053–1057
  38. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20:649–688
  39. Yamazaki K, Shimizu M, Okuno M, et al. Synergistic effects of RXR{alpha} and PPAR{gamma} ligands to inhibit growth in human colon cancer cells phosphorylated RXR{alpha} is a critical target for colon cancer management. Gut. 2007;56:1557–1563
  40. Xiao JH, Ghosn C, Hinchman C, et al. Adenomatous polyposis coli (APC)-independent regulation of beta-catenin degradation via a retinoid X receptor-mediated pathway. J Biol Chem. 2003;278:29954–29962
  41. Faivre J, Boutron MC, Quiport V. Diet and large bowel cancer. In:  Zappia V editors. Advances in nutrition and cancer. New York: Plenum Press; 1993;p. 107–108
  42. Lipkin M, Reddy B, Newmark H, et al. Dietary factors in human colorectal cancer. Annu Rev Nutr. 1999;19:545–586
  43. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434:843–850

 Conflicts of interest The authors disclose no conflicts.

 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).

PII: S0016-5085(09)01755-7

doi: 10.1053/j.gastro.2009.09.060

Gastroenterology
Volume 138, Issue 2 , Pages 636-648.e12 , February 2010

Article Tools

* Image Usage & Resolution