Article

RUNX3 protein is overexpressed in human basal cell carcinomas.

Department of Pathology, National University Hospital, Yong Loo Lin Medical School, National University of Singapore (NUS), Singapore, Singapore.
Oncogene (impact factor: 6.37). 01/2007; 25(58):7646-9. DOI:10.1038/sj.onc.1209739 pp.7646-9
Source: PubMed

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 beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-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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Keywords

75 paired BCC
 
Basal cell carcinomas
 
BCC cases
 
bone morphogenetic protein/transforming growth factor-beta pathways
 
certain human cancers
 
constitutively active Shh pathway
 
deregulation
 
DNA sequencing
 
implicating RUNX3
 
nuclear accumulation
 
nuclear effectors
 
overexpressed protein
 
RUNX3 protein uniformly overexpressed
 
Shh pathway
 
skin malignancy
 
Sonic Hedgehog
 
tissue microarray
 
unique model
 
varying subcellular expression pattern
 
Wnt signalling