COX-2 gene expression and CpG islands methylation in human hepatocelular carcinoma

FERNÁNDEZ ALVAREZ, ANA JULIA; LLORENTE-IZQUIERDO, ANA C.; MARIN-SANZ, PALOMA; CASADO PINNA, MARTA

Torino

Congreso; 36th FEBS Congress; 2011

Federation of European Biochemical Societies (FEBS)

Cyclooxygenase (COX) is a key regulatory step in the biosynthesis of prostaglandins, which are implicated in cell homeostatic processes and play an important role in the onset of inflammation, mitogenic responses and cancer. COX-2 is expressed and induced by different stimuli in several tissues and cellular types. COX-2 expression in liver is restricted to those situations in which proliferation or dedifferentiation occurs. Previous reports suggest that COX-2 signaling is implicated in hepatocelular carcinoma (HCC). Although COX-2 expression is elevated in the early stages of HCC, there is an inverse correlation between COX-2 expression and the differentiation grade of HCC. Moreover, our preliminary results reported that COX-2 mRNA expression was significantly higher in the adjacent liver than in HCC. Epigenetic modifications of genomic DNA underlie regulation of all genome functions, including gene expression, DNA replication and genome stability. Particularly, CpG islands methylation is associated with suppression of gene expression. Promoter hypermethylation transcriptionally silences COX-2 in HCC cells showing that epigenetic alteration of COX-2, at least in part, modulates the growth of HCC cells. In order to determine the implication of epigenetic events in liver cancer progression we studied the CpG island methylation on COX-2 gene by pyrosequencing in several human HCC samples. We have performed the study including DNA obtained from non- tumor and tumor cells of each patient biopsy. The results allow a detailed analysis of the correlation between the CpG methylation status, the COX-2 mRNA expression and the histological classification of HCC.