Molecular Diagnostics

British Journal of Cancer (2007) 96, 1896–1903. doi:10.1038/sj.bjc.6603818 www.bjcancer.com
Published online 22 May 2007

Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups

F Mansilla1,5, K Birkenkamp-Demtroder1,5, M Kruhøffer1, F B Sørensen2, C L Andersen1, P Laiho3, L A Aaltonen3, H W Verspaget4 and T F Ørntoft1

  1. 1Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej 100, DK-8200 Århus N, Denmark
  2. 2Department of Pathology, Aarhus University Hospital, Århus, Denmark
  3. 3Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, Finland;
  4. 4Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence: Dr K Birkenkamp-Demtroder, E-mail: kbdr@ki.au.dk

5These authors contributed equally to this work.

Received 3 November 2006; Revised 30 April 2007; Accepted 30 April 2007; Published online 22 May 2007.

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Abstract

Microarray analysis on pooled samples has previously identified ZDHHC9 (DHHC9) to be upregulated in colon adenocarcinoma compared to normal colon mucosa. Analyses of 168 samples from proximal and distal adenocarcinomas using U133plus2.0 microarrays validated these findings, showing a significant two-fold (log 2) upregulation of DHHC9 transcript (P<10-6). The upregulation was more striking in microsatellite stable (MSS), than in microsatellite instable (MSI), tumours. Genes known to interact with DHHC9 as H-Ras or N-Ras did not show expression differences between MSS and MSI. Immunohistochemical analysis was performed on 60 colon adenocarcinomas, previously analysed on microarrays, as well as on tissue microarrays with 40 stage I–IV tumours and 46 tumours from different organ sites. DHHC9 protein was strongly expressed in MSS compared to MSI tumours, readily detectable in premalignant lesions, compared to the rare expression seen in normal mucosa. DHHC9 was specific for tumours of the gastrointestinal tract and localised to the Golgi apparatus, in vitro and in vivo. Overexpression of DHHC9 decreased the proliferation of SW480 and CaCo2 MSS cell lines significantly. In conclusion, DHHC9 is a gastrointestinal-related protein highly expressed in MSS colon tumours. The palmitoyl transferase activity, modifying N-Ras and H-Ras, suggests DHHC9 as a target for anticancer drug design.

Keywords:

DHHC9, immunohistochemistry, microarray, microsatellite instability