The upregulation of metallothionein-1 expression in areca quid chewing-associated oral squamous cell carcinomas.
Oral Oncol
; 44(2): 180-6, 2008 Feb.
Article
en En
| MEDLINE
| ID: mdl-17418620
ABSTRACT
Metallothioneins (MTs) are a family of low molecular weight, cysteine-rich, inducible, intracellular proteins that bind heavy metals with high affinity. MT-1 is known as a stress-inducible protein and functions as an antioxidant enzyme. Areca quid chewing is a major risk factor in the development and further progression of oral squamous cell carcinoma (OSCC). The aim of this study was to compare MT-1 expression in normal human oral epithelium and OSCC and further explore the potential mechanism that may lead to induce MT-1 expression. Thirty four OSCC and 10 normal epithelium specimens were examined by immunohistochemistry and analyzed by the clinico-pathological profiles. The oral epithelial cell line GMN cells were challenged with arecoline, a major areca nut alkaloid, by reverse-transcriptase polymerase chain reaction. Furthermore, tobacco smoke carcinogen benzo[a]pyrene (BaP) and glutathione (GSH) precursor N-acetyl-l-cysteine (NAC) were added to find the possible regulatory mechanisms. The results from immunohistochemistry demonstrated that MT-1 expression was significantly higher in OSCC specimens (p<0.05). No significant difference in MT-1 expression was observed with respect to age, sex, T category, and stage (p>0.05). The high MT-1 expression was associated with lymph node metastasis (p=0.012). In addition, arecoline was found to elevate MT-1 mRNA in a dose-dependent manner (p<0.05). Furthermore, the addition of BaP enhanced the arecoline-induced MT-1 expression (p<0.05). The addition of NAC markedly inhibited the arecoline-induced MT-1 expression (p<0.05). These results lead to the conclusion that MT-1 expression is significantly upregulated in areca quid chewing associated-OSCC. The expression profile suggests MT-1 could be used clinically as a marker for tumors possessing the potential for lymph node metastasis. The compounds of tobacco products may act synergistically in the pathogenesis of OSCC in areca quid chewers. The regulation of MT-1 expression induced by arecoline is critically dependent on the intracellular GSH concentration.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Areca
/
Neoplasias de la Boca
/
Carcinoma de Células Escamosas
/
Regulación hacia Arriba
/
Metalotioneína
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Oral Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2008
Tipo del documento:
Article
País de afiliación:
Taiwán