...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Deregulated minichromosomal maintenance protein MCM7 contributes to oncogene driven tumorigenesis
【24h】

Deregulated minichromosomal maintenance protein MCM7 contributes to oncogene driven tumorigenesis

机译：失控的微型染色体维持蛋白MCM7促癌基因驱动的肿瘤发生

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Minichromosomal maintenance protein 7 (MCM7) is an essential component of the replication helicase complex (MCM2-7) required for DNA replication. Although this function is highly conserved among eukaryotes, additional functions for the MCM molecules continue to be described. Minichromosomal maintenance protein 7 is a marker for proliferation and is upregulated in a variety of tumors including neuroblastoma, prostate, cervical and hypopharyngeal carcinomas. To further investigate the general role of MCM7 in tumorigenesis, we generated a mouse model with deregulated MCM7 expression targeted to the basal layer of the epidermis using the keratin 14 (K14) promoter (K14.MCM7). When subjected to a two-stage chemical carcinogenesis protocol (dimethylbenz[]anthracene (DMBA) initiation with 12-ortho-tetradecanoylphorbol-13-acetate promotion), K14.MCM7 mice showed significantly increased incidence and prevalence of tumor development relative to controls. Furthermore, within 40 weeks of treatment over 45% K14.MCM7 mice exhibited tumors that had converted to squamous cell carcinomas versus none in the control group. As predicted from previous skin carcinogenesis studies using DMBA as the initiating agent, Ras mutations where found in more than 90% of tumors isolated from K14.MCM7 mice. Whereas previous studies have shown that MCM7 is useful as a proliferation marker, our data suggest that deregulated MCM7 expression actively contributes to tumor formation, progression and malignant conversion.
机译：微型染色体维持蛋白7（MCM7）是DNA复制所需的复制解旋酶复合物（MCM2-7）的重要组成部分。尽管此功能在真核生物中高度保守，但继续描述MCM分子的其他功能。微型染色体维持蛋白7是增殖的标志物，在包括神经母细胞瘤，前列腺癌，子宫颈癌和下咽癌在内的多种肿瘤中被上调。为了进一步研究MCM7在肿瘤发生中的一般作用，我们使用角蛋白14（K14）启动子（K14.MCM7）生成了靶向表皮基底层的MCM7表达失控的小鼠模型。当经历一个两阶段的化学致癌方案（用十二-正十四烷酰佛波醇-13-乙酸盐促进的二甲基苯并[蒽]（DMBA）引发）时，相对于对照，K14.MCM7小鼠显示出显着增加的肿瘤发生率和患病率。此外，在治疗的40周内，超过45％的K14.MCM7小鼠表现出已转化为鳞状细胞癌的肿瘤，而对照组则没有。正如以前使用DMBA作为引发剂的皮肤癌变研究中所预测的，在90％以上的K14.MCM7小鼠肿瘤中发现了Ras突变。尽管先前的研究表明MCM7可用作增殖标记物，但我们的数据表明MCM7表达失活会积极促进肿瘤的形成，进展和恶性转化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号