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dc.contributor.authorKaiser, Sergio
dc.contributor.authorPark, Young-Kyu
dc.contributor.authorFranklin, Jeffrey
dc.contributor.authorHalberg, Richard
dc.contributor.authorYu, Ming
dc.contributor.authorJessen, Walter
dc.contributor.authorFreudenberg, Johannes
dc.contributor.authorChen, Xiaodi
dc.contributor.authorHaigis, Kevin
dc.contributor.authorJegga, Anil
dc.contributor.authorKong, Sue
dc.contributor.authorSakthivel, Bhuvaneswari
dc.contributor.authorXu, Huan
dc.contributor.authorReichling, Timothy
dc.contributor.authorAzhar, Mohammad
dc.contributor.authorBoivin, Gregory
dc.contributor.authorRoberts, Reade
dc.contributor.authorBissahoyo, Anika
dc.contributor.authorGonzales, Fausto
dc.contributor.authorBloom, Greg
dc.contributor.authorEschrich, Steven
dc.contributor.authorCarter, Scott
dc.contributor.authorAronow, Jeremy
dc.contributor.authorKleimeyer, John
dc.contributor.authorKleimeyer, Michael
dc.contributor.authorRamaswamy, Vivek
dc.contributor.authorSettle, Stephen
dc.contributor.authorBoone, Braden
dc.contributor.authorLevy, Shawn
dc.contributor.authorGraff, Jonathan
dc.date.accessioned2016-05-20T08:59:33Z
dc.date.available2016-05-20T08:59:33Z
dc.date.issued2007en
dc.identifier.citationGenome Biology 2007, 8:R131 (doi:10.1186/gb-2007-8-7-r131)en
dc.identifier.doi10.1186/gb-2007-8-7-r131en
dc.identifier.urihttp://hdl.handle.net/10150/610145
dc.description.abstractBACKGROUND:The expression of carcino-embryonic antigen by colorectal cancer is an example of oncogenic activation of embryonic gene expression. Hypothesizing that oncogenesis-recapitulating-ontogenesis may represent a broad programmatic commitment, we compared gene expression patterns of human colorectal cancers (CRCs) and mouse colon tumor models to those of mouse colon development embryonic days 13.5-18.5.RESULTS:We report here that 39 colon tumors from four independent mouse models and 100 human CRCs encompassing all clinical stages shared a striking recapitulation of embryonic colon gene expression. Compared to normal adult colon, all mouse and human tumors over-expressed a large cluster of genes highly enriched for functional association to the control of cell cycle progression, proliferation, and migration, including those encoding MYC, AKT2, PLK1 and SPARC. Mouse tumors positive for nuclear beta-catenin shifted the shared embryonic pattern to that of early development. Human and mouse tumors differed from normal embryonic colon by their loss of expression modules enriched for tumor suppressors (EDNRB, HSPE, KIT and LSP1). Human CRC adenocarcinomas lost an additional suppressor module (IGFBP4, MAP4K1, PDGFRA, STAB1 and WNT4). Many human tumor samples also gained expression of a coordinately regulated module associated with advanced malignancy (ABCC1, FOXO3A, LIF, PIK3R1, PRNP, TNC, TIMP3 and VEGF).CONCLUSION:Cross-species, developmental, and multi-model gene expression patterning comparisons provide an integrated and versatile framework for definition of transcriptional programs associated with oncogenesis. This approach also provides a general method for identifying pattern-specific biomarkers and therapeutic targets. This delineation and categorization of developmental and non-developmental activator and suppressor gene modules can thus facilitate the formulation of sophisticated hypotheses to evaluate potential synergistic effects of targeting within- and between-modules for next-generation combinatorial therapeutics and improved mouse models.
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://genomebiology.com/2007/8/7/R131en
dc.rights© 2007 Kaiser et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleTranscriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon canceren
dc.typeArticleen
dc.contributor.departmentBiomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USAen
dc.contributor.departmentDepartments of Medicine, and Cell and Developmental Biology, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232, USAen
dc.contributor.departmentMcArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USAen
dc.contributor.departmentDepartment of Genetics and Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USAen
dc.contributor.departmentMolecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USAen
dc.contributor.departmentDivision of Human Cancer Genetics, The Ohio State University College of Medicine, Columbus, Ohio 43210-2207, USAen
dc.contributor.departmentInstitute for Collaborative BioResearch, University of Arizona, Tucson, AZ 85721-0036, USAen
dc.contributor.departmentUniversity of Cincinnati, Department of Pathology and Laboratory Medicine, Cincinnati, OH 45267, USAen
dc.contributor.departmentH Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USAen
dc.contributor.departmentChildren's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, Massachusetts 02115, USAen
dc.contributor.departmentUniversity of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USAen
dc.identifier.journalGenome Biologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-08-20T14:18:29Z
html.description.abstractBACKGROUND:The expression of carcino-embryonic antigen by colorectal cancer is an example of oncogenic activation of embryonic gene expression. Hypothesizing that oncogenesis-recapitulating-ontogenesis may represent a broad programmatic commitment, we compared gene expression patterns of human colorectal cancers (CRCs) and mouse colon tumor models to those of mouse colon development embryonic days 13.5-18.5.RESULTS:We report here that 39 colon tumors from four independent mouse models and 100 human CRCs encompassing all clinical stages shared a striking recapitulation of embryonic colon gene expression. Compared to normal adult colon, all mouse and human tumors over-expressed a large cluster of genes highly enriched for functional association to the control of cell cycle progression, proliferation, and migration, including those encoding MYC, AKT2, PLK1 and SPARC. Mouse tumors positive for nuclear beta-catenin shifted the shared embryonic pattern to that of early development. Human and mouse tumors differed from normal embryonic colon by their loss of expression modules enriched for tumor suppressors (EDNRB, HSPE, KIT and LSP1). Human CRC adenocarcinomas lost an additional suppressor module (IGFBP4, MAP4K1, PDGFRA, STAB1 and WNT4). Many human tumor samples also gained expression of a coordinately regulated module associated with advanced malignancy (ABCC1, FOXO3A, LIF, PIK3R1, PRNP, TNC, TIMP3 and VEGF).CONCLUSION:Cross-species, developmental, and multi-model gene expression patterning comparisons provide an integrated and versatile framework for definition of transcriptional programs associated with oncogenesis. This approach also provides a general method for identifying pattern-specific biomarkers and therapeutic targets. This delineation and categorization of developmental and non-developmental activator and suppressor gene modules can thus facilitate the formulation of sophisticated hypotheses to evaluate potential synergistic effects of targeting within- and between-modules for next-generation combinatorial therapeutics and improved mouse models.


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