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Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia

Oncogene volume 25, pages 3445–3457 (2006)Cite this article

Abstract

Achaete-scute like (ASCL)2 is a basic helix–loop–helix transcription factor essential for the maintenance of proliferating trophoblasts during placental development. Using oligonucleotide microarrays we identified ascl2 as a gene significantly upregulated in colorectal adenocarcinomas (n=36 cancers, n=16 normals; 15-fold, P<0.0001). This finding was confirmed by quantitative reverse transcriptase (RT)–PCR on large intestinal cancers (n=29 cancers, n=16 normals; 10-fold, P<0.0001). In situ hybridization for ascl2 demonstrated expression at the base of small and large intestinal crypts (n=304), but in no other normal tissues excepting placenta. By in situ hybridization, 52–71% of colorectal adenomas (n=187), 50–73% of large (n=327) and 33–64% of small intestinal adenocarcinomas (n=124) were positive for ascl2 expression. Upregulation of murine ascl2 was also observed using oligonucleotide microarrays, quantitative RT–PCR and in situ hybridization on apcmin/+ and apc1638N/+ smad4−/+ tumours. Tumour cell lines stably transfected with LEF1DN or APC2, or transiently transfected with short-interfering RNA (siRNA) against β-catenin showed a significant downregulation of ascl2. Colocalization of ascl2 with nuclear β-catenin was observed in 73 small intestinal adenocarcinomas (P=0.0008) and apcmin/+ tumours. Preliminary in vitro data suggest ascl2 may promote progression through the G2/M cell cycle checkpoint. In summary, ascl2 is a putative regulator of proliferation that is overexpressed in intestinal neoplasia.

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Authors and Affiliations

  1. Department of Pathology, Genentech Inc., South San Francisco, CA, USA

    A M Jubb, S Chalasani, G D Frantz, K J Hillan & H Koeppen

  2. Academic Unit of Pathology, St James' Hospital, Leeds, UK

    A M Jubb, H I Grabsch, V Kavi, N J Maughan & P Quirke

  3. Erasmus University Medical Center, Rotterdam, The Netherlands

    R Smits

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  1. A M Jubb
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  2. S Chalasani
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Correspondence to A M Jubb.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Jubb, A., Chalasani, S., Frantz, G. et al. Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia. Oncogene 25, 3445–3457 (2006). https://doi.org/10.1038/sj.onc.1209382

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