Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis.
Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis.
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发表时间：
2003-08
期刊：
影响因子：
11.2
通讯作者：
R. Riley;S. Duensing;T. Brake;K. Münger;P. Lambert;J. Arbeit
中科院分区：
文献类型：
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作者：
R. Riley;S. Duensing;T. Brake;K. Münger;P. Lambert;J. Arbeit
人宫颈癌是由编码E6和E7癌蛋白的高危人乳头瘤病毒引起的，E6和E7癌蛋白中的每一种改变调节细胞周期、凋亡和分化的不同靶点的功能。在这里，我们确定了E6或E7的分子贡献的肿瘤进展和恶性生长的转基因小鼠模型的宫颈癌。E7增加了增殖和中心体拷贝数，并导致多灶性微侵袭性宫颈癌的进展。E6升高了中心体拷贝数，消除了可检测到的p53蛋白，但不产生肿瘤或癌症。E6加E7还增加了中心体拷贝数，并产生了大的、广泛浸润的癌症。中心体拷贝数增加和p53丢失可能导致恶性生长;然而，增殖和分化失调是致癌进展所必需的。
Human cervix cancer is caused by high-risk human papillomaviruses encoding E6 and E7 oncoproteins, each of which alter function of distinct targets regulating the cell cycle, apoptosis, and differentiation. Here we determined the molecular contribution of E6 or E7 to neoplastic progression and malignant growth in a transgenic mouse model of cervical carcinogenesis. E7 increased proliferation and centrosome copy number, and produced progression to multifocal microinvasive cervical cancers. E6 elevated centrosome copy number and eliminated detectable p53 protein, but did not produce neoplasia or cancer. E6 plus E7 additionally elevated centrosome copy number and created large, extensively invasive cancers. Centrosome copy number increases and p53 loss likely contributed to malignant growth; however, dysregulated proliferation and differentiation were required for carcinogenic progression.