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

Francisco Mansilla, Karin Birkenkamp-Demtröder, Mogens Kruhøffer, Flemming B Sørensen, Claus Lindbjerg Andersen, Päivi Laiho, Lauri A Aaltonen, H. W Verspaget, Torben F Ørntoft

    Research output: Contribution to journalArticleScientificpeer-review

    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."
    Original languageEnglish
    JournalBritish Journal of Cancer
    Volume96
    Issue number12
    Pages (from-to)1896-1903
    Number of pages8
    ISSN0007-0920
    DOIs
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Mansilla, F., Birkenkamp-Demtröder, K., Kruhøffer, M., Sørensen, F. B., Andersen, C. L., Laiho, P., ... Ørntoft, T. F. (2007). Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups. British Journal of Cancer, 96(12), 1896-1903. https://doi.org/10.1038/sj.bjc.6603818
    Mansilla, Francisco ; Birkenkamp-Demtröder, Karin ; Kruhøffer, Mogens ; Sørensen, Flemming B ; Andersen, Claus Lindbjerg ; Laiho, Päivi ; Aaltonen, Lauri A ; Verspaget, H. W ; Ørntoft, Torben F. / Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups. In: British Journal of Cancer. 2007 ; Vol. 96, No. 12. pp. 1896-1903.
    @article{570fbacda8a44f06a75bac5a2b9fb39e,
    title = "Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups",
    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 = "311 Basic medicine",
    author = "Francisco Mansilla and Karin Birkenkamp-Demtr{\"o}der and Mogens Kruh{\o}ffer and S{\o}rensen, {Flemming B} and Andersen, {Claus Lindbjerg} and P{\"a}ivi Laiho and Aaltonen, {Lauri A} and Verspaget, {H. W} and {\O}rntoft, {Torben F}",
    year = "2007",
    doi = "10.1038/sj.bjc.6603818",
    language = "English",
    volume = "96",
    pages = "1896--1903",
    journal = "British Journal of Cancer",
    issn = "0007-0920",
    publisher = "Nature Publishing Group",
    number = "12",

    }

    Mansilla, F, Birkenkamp-Demtröder, K, Kruhøffer, M, Sørensen, FB, Andersen, CL, Laiho, P, Aaltonen, LA, Verspaget, HW & Ørntoft, TF 2007, 'Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups', British Journal of Cancer, vol. 96, no. 12, pp. 1896-1903. https://doi.org/10.1038/sj.bjc.6603818

    Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups. / Mansilla, Francisco; Birkenkamp-Demtröder, Karin; Kruhøffer, Mogens; Sørensen, Flemming B; Andersen, Claus Lindbjerg; Laiho, Päivi; Aaltonen, Lauri A; Verspaget, H. W; Ørntoft, Torben F.

    In: British Journal of Cancer, Vol. 96, No. 12, 2007, p. 1896-1903.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups

    AU - Mansilla, Francisco

    AU - Birkenkamp-Demtröder, Karin

    AU - Kruhøffer, Mogens

    AU - Sørensen, Flemming B

    AU - Andersen, Claus Lindbjerg

    AU - Laiho, Päivi

    AU - Aaltonen, Lauri A

    AU - Verspaget, H. W

    AU - Ørntoft, Torben F

    PY - 2007

    Y1 - 2007

    N2 - "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."

    AB - "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."

    KW - 311 Basic medicine

    U2 - 10.1038/sj.bjc.6603818

    DO - 10.1038/sj.bjc.6603818

    M3 - Article

    VL - 96

    SP - 1896

    EP - 1903

    JO - British Journal of Cancer

    JF - British Journal of Cancer

    SN - 0007-0920

    IS - 12

    ER -

    Mansilla F, Birkenkamp-Demtröder K, Kruhøffer M, Sørensen FB, Andersen CL, Laiho P et al. Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups. British Journal of Cancer. 2007;96(12):1896-1903. https://doi.org/10.1038/sj.bjc.6603818