Study of MAGE gene in Bladder Cancer

(1)在bbn诱导的小鼠膀胱癌模型中，未发现Mage-a基因的突变改变。假设在正常组织中沉默的Mage-a基因在小鼠膀胱癌中被激活，其激活机制可能归因于转录后或翻译后事件。Tcf-4/β-catenin通路（Wnt信号）在小鼠膀胱癌模型中对癌变的影响较低，在大肠癌和肝癌中参与肿瘤发生的影响较小。另外，Mage-a基因的改变直接影响Wnt信号通路激活的可能性也不大。(2)在临床获得的膀胱癌标本中，MAGE-1 mRNA的表达与VEGF-121、VEGF-165和肝素酶mRNA各亚型的表达水平呈正相关，表明MAGE-1的表达不仅与肿瘤血管生成有关，还与肿瘤侵袭和/或转移有关。反过来，有证据表明表达MAGE-1 mRNA的膀胱癌患者与不表达肝素酶mRNA的膀胱癌患者相比，无进展概率较低，这一事实也支持了这一事实。另一方面，尽管Tcf-4/β-catenin的激活偶有发生在膀胱癌中，但MAGE-1 mRNA的表达可能与Wnt信号通路的激活间接相关。此外，MMP-1启动子区域的单核苷酸多态性似乎与MAGE-1 mRNA的表达无关。总之，MAGE-1 mRNA的表达有望为膀胱癌的肿瘤生物学研究提供新的思路。

(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.