Abstract
Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of β-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-β pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of β-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.
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Acknowledgements
This work was supported by the Agency for Science, Technology and Research (A*STAR), Singapore. M Salto-Tellez and SH Tan are recipients of Singapore Cancer Syndicate Grants MN005 and BS002, Agency for Science, Technology and Research, Singapore.
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Salto-Tellez, M., Peh, B., Ito, K. et al. RUNX3 protein is overexpressed in human basal cell carcinomas. Oncogene 25, 7646–7649 (2006). https://doi.org/10.1038/sj.onc.1209739
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DOI: https://doi.org/10.1038/sj.onc.1209739
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