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Study of MAGE gene in Bladder Cancer

MAGE基因在膀胱癌中的研究

基本信息

批准号：
10671473
负责人：
SHIINA Hiroaki
金额：
$ 2.11万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671473/
关键词：
bladder cancer TRA MAGE gene biological behavior angiogenesis 腫瘍拒絶抗原増殖能 p53遺伝子

项目摘要

(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.

(1)在BBN诱导的小鼠膀胱癌模型中，未发现Mage-a基因的突变，但在正常组织中沉默的Mage-a基因在小鼠膀胱癌中被激活，其激活机制可能是转录后或翻译后事件。Tcf-4/β-catenin信号通路（Wnt信号）在膀胱癌模型中的临床意义与在大肠癌和肝癌中观察到的肿瘤发生相比，其对肿瘤发生的影响较小。另外，Mage-a基因的改变不太可能直接影响Wnt信号通路的激活。(2)在临床获得的膀胱癌标本中，法师-1 mRNA的表达与VEGF-121和VEGF-165的每种亚型以及乙酰肝素酶mRNA的水平呈正相关，表明法师-1表达不仅与肿瘤血管生成有关，而且与肿瘤侵袭和/或转移有关。反过来，这一事实得到以下证据的支持：与不表达乙酰肝素酶mRNA的膀胱癌患者相比，表达法师-1 mRNA的膀胱癌患者无进展概率低。另一方面，虽然Tcf-4/β-catenin在膀胱癌中偶尔发生激活，但法师-1 mRNA的表达可能与Wnt信号通路的激活间接相关。此外，MMP-1启动子区的单核苷酸多态性似乎与法师-1 mRNA的表达无关。总之，法师-1 mRNA的表达有望为膀胱癌的肿瘤生物学研究提供新的视角。