Genomic Instability Induced By Human Papillomavirus Oncogenes.
Genomic Instability Induced By Human Papillomavirus Oncogenes.
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DOI：
10.7156/v3i2p043
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
Chen JJ
中科院分区：
文献类型：
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作者：
Chen JJ
宫颈癌是全世界妇女癌症死亡的主要原因之一。人乳头瘤病毒（HPV）感染是必要的，但不是宫颈癌发展的充分条件。由HPV引起的基因组不稳定允许细胞获得恶性转化所需的额外突变。多倍体形式的基因组不稳定性与宫颈癌发生的因果关系有关。多倍体不仅作为宫颈癌发生的早期事件发生，而且还使宫颈细胞易发生非整倍体，这是人类癌症的重要标志。细胞周期进程在几个检查点受到调控，这些检查点的缺陷导致基因组不稳定。高危hpv编码两个致癌基因E6和E7，这两个基因对于hpv阳性细胞的细胞转化至关重要。高风险的HPV E6和E7蛋白分别促进p53和pRb降解的能力已被认为是HPV癌基因诱导细胞转化的机制。E6和E7取消细胞周期检查点，诱导基因组不稳定，导致恶性转化。虽然预防性HPV疫苗最近已经可用，但它对免疫抑制的个体或已经感染的人无效。因此，了解hpv相关癌症的分子基础仍具有临床意义。对基因组不稳定性的研究将揭示HPV诱导癌症的机制，并为确定药物开发的目标提供希望。
Cervical cancer is one of the leading causes of cancer death in women worldwide. Human papillomavirus (HPV) infection is necessary but not sufficient for the development of cervical cancer. Genomic instability caused by HPV allows cells to acquire additional mutations required for malignant transformation. Genomic instability in the form of polyploidy has been implicated in a causal role in cervical carcinogenesis. Polyploidy not only occurs as an early event during cervical carcinogenesis but also predisposes cervical cells to aneuploidy, an important hallmark of human cancers. Cell cycle progression is regulated at several checkpoints whose defects contribute to genomic instability. The high-risk HPVs encode two oncogenes, E6 and E7, which are essential for cellular transformation in HPV-positive cells. The ability of high-risk HPV E6 and E7 protein to promote the degradation of p53 and pRb, respectively, has been suggested as a mechanism by which HPV oncogenes induce cellular transformation. E6 and E7 abrogate cell cycle checkpoints and induce genomic instability that leads to malignant conversion. Although the prophylactic HPV vaccine has recently become available, it will not be effective for immunosuppressed individuals or those who are already infected. Therefore, understanding the molecular basis for HPV-associated cancers is still clinically relevant. Studies on genomic instability will shed light on mechanisms by which HPV induces cancer and hold promise for the identification of targets for drug development.