1. Phosphoprotein Keratin 23 accumulates in MSS but not MSI colon cancers in vivo and impacts viability and proliferation in vitro
- Author
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Birkenkamp-Demtroder, Karin, Mansilla, Francisco, Sørensen, Flemming Brandt, Kruhøffer, Mogens, Cabezón, Teresa, Christensen, Lise Lotte, Aaltonen, Lauri A., Verspaget, Hein W., and Falck Ørntoft, Torben
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COLON cancer , *CANCER invasiveness , *CANCER cells , *MUCOUS membranes , *ADENOCARCINOMA , *MICROSATELLITE repeats - Abstract
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 46.8kDa 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. [Copyright &y& Elsevier]
- Published
- 2007
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