title: Phosphoprotein Keratin 23 accumulates in MSS but not MSI colon cancers in vivo and impacts viability and proliferation in vitro.
abstract: Transcript profiling of 27 normal colon mucosas and 258 adenocarcinomas showed Keratin23 to be increased in 78% microsatellite-stable tumors, while microsatellite-instable tumors showed low transcript levels, comparable to normal mucosas. Immunohistochemical analyses demonstrated that 88% of microsatellite-instable tumors were negative for Keratin23 protein, while 70% of MSS tumors and metastases derived from MSS-tumors showed high Keratin23 levels. Immunofluorescence analysis localized Keratin23 in the Golgi-apparatus. Golgi accumulation was unique for gastrointestinal adenocarcinomas. Immunoprecipitation and 2D-blot analysis revealed Keratin23 to be a 46.8 kDa phosphoprotein. Keratin23 impaired the proliferation of human colon cancer cells significantly, leading to cell death in microsatellite-instable but not microsatellite-stable cell lines, while COS7 cells experienced multiple nuclei and apoptosis. Keratin23 expression correlated significantly with transcription factor CEBPB. In conclusion, Keratin23 expression is a novel and important difference between microsatellite-stable and microsatellite-instable colon cancers.
authors.affiliation: Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. kbdr@ki.au.dk
authors.forename: Karin
authors.initials: K
authors.lastname: Birkenkamp-Demtroder
authors.forename: Francisco
authors.initials: F
authors.lastname: Mansilla
authors.forename: Flemming Brandt
authors.initials: FB
authors.lastname: Sørensen
authors.forename: Mogens
authors.initials: M
authors.lastname: Kruhøffer
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabezón
authors.forename: Lise Lotte
authors.initials: LL
authors.lastname: Christensen
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Hein W
authors.initials: HW
authors.lastname: Verspaget
authors.forename: Torben Falck
authors.initials: TF
authors.lastname: Ørntoft
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D053530:Keratins, Type I / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C420247:KRT23 protein, human; D053530:Keratins, Type I; D009363:Neoplasm Proteins; D010750:Phosphoproteins