Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation.
Br J Dermatol
; 151(1): 157-64, 2004 Jul.
Article
en En
| MEDLINE
| ID: mdl-15270885
ABSTRACT
BACKGROUND:
Virtually all BCCs have deregulation of the Hedgehog (Hh) signalling pathway and a proportion show nuclear beta-catenin accumulation. The latter is thought to be due to Hh pathway-directed Wnt expression but this has not been tested. An alternative cause of nuclear beta-catenin accumulation is gene mutation, which stabilizes the protein. Theoretically, reduced E-cadherin expression could also be important because it can sequester beta-catenin at the cell membrane. In turn, nuclear beta-catenin can increase expression of MYC and cyclin D1, thus potentially altering proliferation.OBJECTIVES:
To assess whether nuclear beta-catenin occurs in BCC, and to look at potential causes and consequences.METHODS:
Nuclear beta-catenin was assessed by immunohistochemistry, and its causes by analysis of E-cadherin expression, beta-catenin exon 3 mutation and WNT5A expression. Its consequences were assessed by analysing proliferation.RESULTS:
We found nuclear beta-catenin in 20 of 86 paraffin-embedded sections of BCCs using immunohistochemistry. BCCs showed increased WNT5A relative to the surrounding skin. No mutations in exon 3 of the beta-catenin gene were found in 10 cases. There was no association between beta-catenin localization and E-cadherin expression. Tumours with nuclear beta-catenin had significantly higher proliferation (P < 0.01).CONCLUSIONS:
The absence of beta-catenin gene mutations indicate that the Hh pathway-directed Wnt signalling remains the most likely cause of nuclear beta-catenin accumulation in BCC. Additionally, the correlation with increased proliferation is the first evidence that nuclear beta-catenin may have a biological effect. However, a causal link between Hh pathway deregulation, Wnt ligand overexpression, nuclear beta-catenin accumulation and increased proliferation remains to be confirmed.
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Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Carcinoma Basocelular
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Biomarcadores de Tumor
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Transactivadores
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Núcleo Celular
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Proteínas del Citoesqueleto
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Dermatol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Reino Unido