Altered expression of apoptosis biomarkers in human colorectal microadenomas.
Cancer Epidemiol Biomarkers Prev
; 19(2): 351-7, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-20142237
ABSTRACT
Human colorectal microadenomas are considered the earliest detectable premalignant lesions in the colon. They can be identified as aggregates of enlarged crypts with thicker epithelial linings and elongated luminal openings on the colonic mucosal surface after methylene blue staining and observation under a dissecting microscope. Multiple lines of evidence suggest that a central role in neoplastic development is played by the inhibition of apoptosis, followed by disruption of DNA repair. Understanding the early mechanisms of colorectal carcinogenesis may help develop new approaches of colorectal cancer prevention and treatment. The aim of the present study was to quantify poly-ADP ribose polymerase 1 (PARP-1)-positive cells and to evaluate apoptotic control mechanisms through Caspase-3 active and Bcl-2 protein expression in human microadenomas and in normal colorectal mucosa using immunofluorescence techniques coupled with confocal microscopy and immunoblot experiments. The mean percentage of PARP-1-positive epithelial cells was 3.0 +/- 0.37% (SD) and 15.67 +/- 0.40% in microadenoma and in normal mucosa, respectively. Proteins involved in programmed cell death were differently expressed in microadenoma and in normal mucosa. Indeed, by semiquantitative immunofluorescence analysis, confirmed by Western blot, microadenoma showed low levels of Caspase-3 active and high levels of Bcl-2 expression, whereas the opposite was true for normal colorectal mucosa [corrected]. In the stroma of normal colorectal mucosa, fibroblast-like cells and neutrophils were the cells that underwent apoptosis to a greater extent. In conclusion, malfunction of the control mechanisms of programmed cell death seems present in the early stages of colorectal cancer development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Pré-Cancerosas
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Neoplasias Colorretais
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Biomarcadores Tumorais
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Adenoma
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Apoptose
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article