Phosphoprotein Keratin 23 accumulates in MSS but not MSI colon cancers in vivo and impacts viability and proliferation in vitro

Birkenkamp-Demtroder, Karin; Mansilla, Francisco; Sørensen, Flemming Brandt; Kruhøffer, Mogens; Cabezón, Teresa; Christensen, Lise Lotte; Aaltonen, Lauri A.; Verspaget, Hein W.; Falck Ørntoft, Torben

doi:10.1016/j.molonc.2007.05.005

« Previous Next »Molecular Oncology
Volume 1, Issue 2 , Pages 181-195, September 2007

Phosphoprotein Keratin 23 accumulates in MSS but not MSI colon cancers in vivo and impacts viability and proliferation in vitro

Karin Birkenkamp-Demtroder
- Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark
- Corresponding author: Molecular Diagnostic Laboratory, Center for Molecular Clinical Cancer Research CMCC, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. Tel.: +45 8949 5119; fax: +45 8949 6018.
- KBD and FM have contributed equally to this publication.
Francisco Mansilla
- Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark
- KBD and FM have contributed equally to this publication.
Flemming Brandt Sørensen
- Department of Pathology, Aarhus University Hospital, Nørrebrogade, DK-8000 Århus C, Denmark
Mogens Kruhøffer
- Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark
Teresa Cabezón
- Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
Lise Lotte Christensen
- Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark
Lauri A. Aaltonen
- Finnish Cancer Institute, Department of Medical Genetics, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Finland
Hein W. Verspaget
- Department of Gastroenterology-Hepatology, Leiden University Medical Centre, PO Box 9600, NL-2300 RC Leiden, Netherlands
Torben Falck Ørntoft
- Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark

Received 30 March 2007; received in revised form 15 May 2007; accepted 21 May 2007. published online 28 June 2007.

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.