Study of MAGE gene in Bladder Cancer

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(1) In BBN-INDUCED MURINE BLADDER CANCER MODEL, MUTATIONAL CHANGE OF Mage-a gene was not found. Provided that Mage-a gene, which is silent in normal tissue, is activated in murine bladder cancer, the mechanisms for activation might be attributed to the post-transcriptional or post-translational event. Clinical significance of Tcf-4/β-catenin pathway (Wnt signal) has a low impact on carcinogeneis in murine bladder cancer model, as compared with that observed in involvement of tumorigenesis in colorectal and liver cancer. In addition, there might be low possibility that alteration of Mage-a gene affects directly activation of Wnt signaling pathway.(2) In clinically obtained bladder cancer specimens, expression of MAGE-1 mRNA was positively correlated with the levels of each isoform of VEGF-121 and VEGF-165, and heparanase mRNAs, suggesting MAGE-1 expression is related to not only tumor angiogenesis but also tumor invasion and/or metastasis. In turn, this fact was supported by the evidence that bladder cancer patients with expression of MAGE-1 mRNA has a low progression-free probability as compared with those without expression of heparanase mRNA. On the other hand, although activation of Tcf-4/β-catenin occasionally occurs in bladder cancer, it might be possible that expression of MAGE-1 mRNA is indirectly related to the activation of the Wnt signaling pathway, Furthermore, a single nucleotide polymorphism of MMP-1 promoter region did not appear to be associated with the expression of MAGE-1 mRNA. In conclusion, expression of MAGE-1 mRNA promises a new insight into the tumor biology in bladder cancer.