Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 5
Apoptosis associated with reduced Bcl-2 expression in colorectal cancer tumors
Márcia M. Aranha1, Pedro M. Borralho1, Paula Ravasco2, Isabel B. Moreira da Silva1,
Luís Correia3, Afonso Fernandes4, Maria E. Camilo2, Cecília M.P. Rodrigues1
1Centro de Patogénese Molecular, Faculty of Pharmacy, University of Lisbon, 1600-083
Lisbon, Portugal; 2Unidade de Metabolimo e Nutrição, IMM; Centro de
3Gastrenterologia e de 4Anatomia Patológica, Santa Maria Hospital, Lisbon, Portugal;
E-mail: maranha@ff.ul.pt
Compelling evidence implicates loss of cell-cycle control and changes in apoptotic pathways
in the development and progression of most human cancers. In this study, several apoptotic
factors were examined in normal and tumor tissues from patients diagnosed for colorectal
cancer. Apoptosis as assessed by the transferase mediated dUTP-digoxigenin nick-end
labeling (TUNEL) assay was significantly higher in tumor tissue compared with normal
mucosa (p < 0.01). TUNEL-positive cells were increased from adenoma to poorly
differentiated adenocarcinoma, but decreased in association with higher degree of
adenocarcinoma differentiation. Similar results were observed for NF-!B/RelA expression
detected by immunohistochemistry (p < 0.01). Further, Bcl-2 expression was consistently
higher in normal mucosa than in tumor tissue (p < 0.01). In both adenoma and
adenocarcinoma tissues, Bcl-2 immunoreactivity was almost undetectable, which inversely
correlated with the percentage of apoptotic cells (r = - 0.54; p < 0.01). In addition, expression
analysis of phosphorylated p53 and Bax by western blot revealed almost no variation of
protein expression in tumor tissue compared to normal mucosa. These results demonstrate
increased apoptosis in pre-malignant and poorly differentiated malignant tissues. Apoptosis
may proceed through a p53- and Bax-independent fashion but is correlated with suppression
of Bcl-2 expression. The histological progression of colorectal cancer from adenoma to
adenocarcinoma involves also NF-!B activation. Whether these changes are associated with
a better prognosis deserves further investigation. (Supported by Sociedade Portuguesa de
Gastrenterologia, Portugal)
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