Repression of MLH1 and MGMT genes in colon mucosa adjacent to implanted cancer in athymic mouse.
J Exp Clin Cancer Res
; 23(2): 317-23, 2004 Jun.
Article
en En
| MEDLINE
| ID: mdl-15354418
ABSTRACT
Hyperplastic mucosa adjacent to colon cancer, being a reactive change, accelerates cancer progression and its metastasis through expression of angiogenic factors. We investigated promoter methylation in hyperplastic mucosa adjacent to orthotopic KM12SM colon cancer in mice. In the hyperplastic mucosa adjacent to KM12SM tumors in the cecum of athymic mice, reductions in the levels of the mutL homologue 1 (MLH1) and O6-methylguanine-DNA methyltransferase (MGMT) proteins were detected by immunohistochemistry and immunoblotting. To examine the effects of growth factors and cytokines on promoter methylation and repressed expression of the MLH1 and MGMT genes, a rat intestinal epithelial cell line, IEC6, was treated with epidermal growth factor (EGF) and interleukin (IL)-15 for 35 days. Protein levels of MLH1 and MGMT were reduced in EGF- and IL-15-treated IEC6 cells. A methylation-sensitive restriction enzyme assay revealed that CpG methylation was present in the promoter regions of the MLH1 and MGMT genes in DNAs extracted from hyperplastic mucosa adjacent to KM12SM tumors. These findings suggest that promoter CpG methylation affects expression of MLH1 MGMT genes in hyperplastic mucosa adjacent to colon cancer.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
Colon
/
Neoplasias del Colon
/
Metilación de ADN
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O(6)-Metilguanina-ADN Metiltransferasa
/
Mucosa Intestinal
/
Proteínas de Neoplasias
Idioma:
En
Revista:
J Exp Clin Cancer Res
Año:
2004
Tipo del documento:
Article
País de afiliación:
Japón