作者: Françoise Praz , Sandrine Jacob , Mélanie Aguado , David Fallik
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摘要: The DNA mismatch repair (MMR) system is involved in the correction of base/base mismatches and insertion/deletion loops arising during replication. In addition, some MMR components participate recombination double-strand break as well cell cycle regulation apoptosis. inactivation genes, usually hMSH2 or hMLH1, associated with human colorectal cancers responsible for characteristic microsatellite instability (MSI)+ phenotype these tumors. Because assumed to modulate cytotoxicity various chemotherapeutic agents that act upon DNA, our objectives have been define its possible involvement topoisomerase inhibitors. We shown cancer lines defective exhibit an increased sensitivity both camptothecin, a I inhibitor, etoposide, II inhibitor. Sensitivity drugs cannot be predicted by measuring endogenous levels II. Our results also indicate neither p53 status, nor alterations correlate cells On other hand, data showing resistance can achieved functional complementation hMLH1 hMLH1-defective line allowed us establish critical determinant chemosensitivity. Interestingly, observations provide rationale better responsiveness MSI+ tumors CPT-11, camptothecin derivative, which we observed patients metastatic cancers.