Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer.
Biochem Biophys Res Commun
; 441(1): 102-7, 2013 Nov 08.
Article
en En
| MEDLINE
| ID: mdl-24134849
Pancreatic cancer is a highly lethal disease with a poor prognosis; the molecular mechanisms of the development of this disease have not yet been fully elucidated. N-myc downstream regulated gene 2 (NDRG2), one of the candidate tumor suppressor genes, is frequently downregulated in pancreatic cancer, but there has been little information regarding its expression in surgically resected pancreatic cancer specimens. We investigated an association between NDRG2 expression and prognosis in 69 primary resected pancreatic cancer specimens by immunohistochemistry and observed a significant association between poor prognosis and NDRG2-negative staining (P=0.038). Treatment with trichostatin A, a histone deacetylase inhibitor, predominantly up-regulated NDRG2 expression in the NDRG2 low-expressing cell lines (PANC-1, PCI-35, PK-45P, and AsPC-1). In contrast, no increased NDRG2 expression was observed after treatment with 5-aza-2' deoxycytidine, a DNA demethylating agent, and no hypermethylation was detected in either pancreatic cancer cell lines or surgically resected specimens by methylation specific PCR. Our present results suggest that (1) NDRG2 is functioning as one of the candidate tumor-suppressor genes in pancreatic carcinogenesis, (2) epigenetic mechanisms such as histone modifications play an essential role in NDRG2 silencing, and (3) the expression of NDRG2 is an independent prognostic factor in pancreatic cancer.
Palabras clave
5-aza-2' deoxycytidine; 5-aza-dC; AU; B2M; Epigenetic silencing; HDAC; Hypermethylation; MSP; N-myc downstream regulated gene 2; NDRG2; Pancreatic cancer; Prognostic factor; TSA; arbitrary unit; cDNA; complementary DNA; histone deacetylase; methylation-specific PCR; qRT-PCR; quantitative reverse transcription polymerase chain reaction; trichostatin A; ß2-microglobulin
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
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Silenciador del Gen
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Proteínas Supresoras de Tumor
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos