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Dark Aberrant Crypt Foci with activated Wnt pathway are related to tumorigenesis in the colon of AOM-treated rat

DOI: 10.1186/1756-9966-27-26

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Abstract:

Sixty wistar rats were sacrificed at different time points after exposure to azoxymethane and the colons were stained with methylene blue for stereomicroscopic analysis.We found two types of early lesions: classic ACF and dark ACF. Dark ACF were characterized by dark blue staining, mildly enlarged or small compressed crypts that are not elevated from the surrounding epithelium. Large dark ACF and nascent tumors displayed the same surface morphology. Furthermore, dark ACF grew significantly faster than classic ACF and showed dysplasia without hyperplasia. In contrast, classic ACF showed hyperplasia without dysplasia. Dark ACF has significant higher expression rate of β-catenin (100%) and MMP-7 (81.82%) compared with the expression of β-catenin and MMP-7 in classic ACF (4.84% and 7.87%, respectively).Our data indicated that dark ACF is closely related to tumorigenesis while classic ACF is not. Furthermore, Wnt signal pathway was activated during the early period of dark ACF.Aberrant crypt foci (ACF) were first described by Bird and Good. The lesion of ACF is composed of the enlarged crypts that are slightly elevated above the surrounding mucosa and the densely stained crypts with methylene blue [1]. ACF are considered as putative preneoplastic lesions of the colon in both humans and experimental animals [2,3].Although ACF may share some morphologic, genetic, and biochemical features with colonic tumors [4-7], conflicting evidence has also been reported. For example, mutations in the K-ras gene are relatively common in human ACF, but are only detected at a relatively late stage of colon cancer [8-11]. In rat models, although hundreds of ACF are induced per animal by azoxymethane (AOM), and K-ras mutations are frequently observed in those ACF, only a few colon tumors are observed per animal [12-14]. In azoxymethane/dimethylhydrazine-treated rats and in patients with sporadic colorectal cancer, the number of tumors is minuscule compared with the large number of ACF [15],

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