title: Proteins and an inflammatory network expressed in colon tumors.
abstract: The adenomatous polyposis coli (APC) protein is crucial to homeostasis of normal intestinal epithelia because it suppresses the β-catenin/TCF pathway. Consequently, loss or mutation of the APC gene causes colorectal tumors in humans and mice. Here, we describe our use of multidimensional protein identification technology (MudPIT) to compare protein expression in colon tumors to that of adjacent healthy colon tissue from Apc(Min/+) mice. Twenty-seven proteins were found to be up-regulated in colon tumors and 25 were down-regulated. As an extension of the proteomic analysis, the differentially expressed proteins were used as "seeds" to search for coexpressed genes. This approach revealed a coexpression network of 45 genes that is up-regulated in colon tumors. Members of the network include the antibacterial peptide cathelicidin (CAMP), Toll-like receptors (TLRs), IL-8, and triggering receptor expressed on myeloid cells 1 (TREM1). The coexpression network is associated with innate immunity and inflammation, and there is significant concordance between its connectivity in humans versus mice (Friedman: p value = 0.0056). This study provides new insights into the proteins and networks that are likely to drive the onset and progression of colon cancer.
authors.affiliation: Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd., La Jolla, California 92037, United States.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhu
authors.forename: Changming
authors.initials: C
authors.lastname: Fang
authors.forename: Kosi
authors.initials: K
authors.lastname: Gramatikoff
authors.forename: Christina C
authors.initials: CC
authors.lastname: Niemeyer
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Smith
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism*; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016209:Interleukin-8 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D040901:Proteomics / Q000379:methods*; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013053:Spectrophotometry; D051193:Toll-Like Receptors / Q000378:metabolism; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D017931:DNA Primers; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1