Abstract
e14707 Background: Microsatellite instability (MSI) is a common cause for a frameshift mutation in Bax the exon 3 microsatellite region leading to Bax-negative phenotype. However, we found that a unique Bax isoform (BaxΔ2) can be generated in combination of the deletion mutation (from G8 to G7) and alternative splicing. BaxΔ2 is a potent cell death inducer and specific to MSI tumors. Methods: The cell death assay, immunoblotting and immunohistochemisty are used for conducting the experiments. Results: The colon cancer cells with Bax G7, not G8, are selectively sensitive to certain chemotherapeutic drugs, such as 5-FU and Adriamycin. Unlike the parental Baxα, BaxΔ2 does not directly target to mitochondria, rather activates the caspase 8-dependent apoptotic pathway. Conclusions: Our data may provide an explanation that some colon cancer patients with “Bax negative” MSI tumor having a better prognosis and suggest that MSI colon cancer with Bax G7 mutation may potentially have a better response to selective chemotherapeutic drugs.
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