Analyse de l'expression de la caspase-3 et de son transcrit alternatif caspase-3s dans le cancer du sein

Recent studies have shown that some apoptosis markers might constitute predictive factors for tumor progression and response to chemotherapy. The caspase-3 plays a important role in apoptosis and in development. Recently, an alternative splice variant, caspase-3s, antagonist of apoptotic property of caspase-3 has identified. In an attempt to evaluate the role of these two transcripts in breast cancer, we analysed their expression by RT-PCR in several tumor cell lines sensitive and resistant to drugs. Two groups of breast tumors were also analysed: node-negative (N-), and locally advanced (LA) tumors. The results showed that expression of the caspase-3s variant is higher (2 to 3 fold) in breast tumor cell lines than in normal tissues. In addition, the ratio caspase-3s/caspase-3 decreased significantly (P = 0,0277) in cell lines resistant to vinblastine, Taxol, and doxorubicine. In breast tumors, expression of caspase-3s is significantly more important in N- than in LA (P < 0.0001). In each group of tumor, an inverse relation in the expression of the two transcripts was detected (P < 0.0001). Furthermore, patients in LA group with high levels of caspase-3 (P = 0,006) or weak levels of caspase-3s (P = 0,03) were more sensitive to anthracyclines-based treatment. Taken together, these results agree with an antagonist function between the two transcripts of caspase-3, and strongly suggested their implication as a predictive factor in breast cancer.