MCM7 amplification and overexpression are associated with prostate cancer progression
MCM7 amplification and overexpression are associated with prostate cancer progression
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DOI：
10.1038/sj.onc.1209134
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发表时间：
2006-02-01
期刊：
影响因子：
8
通讯作者：
Luo, JH
中科院分区：
文献类型：
--
作者：
Ren, B;Yu, G;Luo, JH
将具有侵袭性特征的前列腺癌的基因组 DNA 谱与匹配的正常 DNA 谱进行比较，以确定在癌细胞中选择性扩增的基因。已鉴定的基因之一 MCM7 是 DNA 复制许可复合体的组成部分，已在人类前列腺组织的 DNA 和蛋白质水平上进行了广泛研究。大约一半的研究前列腺癌标本显示 MCM7 基因扩增，60% 的侵袭性前列腺癌标本 MCM7 蛋白表达增加。 MCM7 的扩增或过度表达与复发、局部侵袭和较差的肿瘤分级显着相关。与仅载体对照相比，MCM7 在人前列腺癌细胞系 DU145 中的组成型表达导致 DNA 合成和细胞增殖显着增加，并且体外细胞侵袭增加。事实上，MCM7 过度表达产生的原发肿瘤比仅载体对照大 12 倍，并导致携带这些肿瘤的小鼠迅速死亡。这些研究表明 MCM7 和 DNA 复制许可基因家族与前列腺癌的进展、生长和侵袭有关。
The genomic DNA profiles of prostate cancers with aggressive features were compared to the profiles of matched normal DNA to identify genes that are selectively amplified in the cancer cells. One of the identified genes, MCM7, which is a component of the DNA replication licensing complex, has been studied extensively both at the DNA and protein levels in human prostate tissues. Approximately half of the prostate cancer specimens studied showed MCM7 gene amplification, and 60% of the aggressive prostate cancer specimens had increased MCM7 protein expression. Amplification or overexpression of MCM7 was significantly associated with relapse, local invasion and a worse tumor grade. Constitutive expression of MCM7 in a human prostate cancer cell line, DU145, resulted in markedly increased DNA synthesis and cell proliferation compared to vector-only controls, and an increased cell invasion in vitro. Indeed, MCM7 overexpression produced primary tumors 12 times larger than vector-only controls and resulted in a rapid demise of mice bearing those tumors. These studies implicate MCM7, and the DNA replication licensing gene family, in prostate cancer progression, growth and invasion.