RUNX3 protein is overexpressed in human basal cell carcinomas.
Oncogene
; 25(58): 7646-9, 2006 Dec 07.
Article
em En
| MEDLINE
| ID: mdl-16767156
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
/
Carcinoma Basocelular
/
Subunidade alfa 3 de Fator de Ligação ao Core
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Oncogene
Ano de publicação:
2006
Tipo de documento:
Article