人乳头瘤病毒16型E6和E7可导致人角质形成细胞出现多倍体并使G2-M期蛋白上调。

Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G2-M-phase proteins.

作者信息

Patel Daksha, Incassati Angela, Wang Nancy, McCance Dennis J

机构信息

Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.

出版信息

Cancer Res. 2004 Feb 15;64(4):1299-306. doi: 10.1158/0008-5472.can-03-2917.

DOI:10.1158/0008-5472.can-03-2917

PMID:14973072

Abstract

Human papillomavirus type 16 proteins E6 and E7 have been shown to cause centrosome amplification and lagging chromosomes during mitosis. These abnormalities during mitosis can result in missegregation of the chromosomes, leading to chromosomal instability. Genomic instability is thought to be an essential part of the conversion of a normal cell to a cancer cell. We now show that E6 and E7 together cause polyploidy in primary human keratinocytes soon after these genes are introduced into the cells. Polyploidy seems to result from a spindle checkpoint failure arising from abrogation of the normal functions of p53 and retinoblastoma family members by E6 and E7, respectively. In addition, E6 and E7 cause deregulation of cellular genes such as Plk1, Aurora-A, cdk1, and Nek2, which are known to control the G(2)-M-phase transition and the ordered progression through mitosis.

摘要

人乳头瘤病毒16型蛋白E6和E7已被证明在有丝分裂期间会导致中心体扩增和染色体滞后。有丝分裂期间的这些异常会导致染色体错误分离，从而导致染色体不稳定。基因组不稳定被认为是正常细胞转变为癌细胞过程中的一个重要部分。我们现在表明，在将E6和E7基因导入原代人角质形成细胞后不久，它们共同导致细胞多倍体化。多倍体似乎是由于E6和E7分别废除了p53和视网膜母细胞瘤家族成员的正常功能而导致纺锤体检查点功能障碍所致。此外，E6和E7会导致细胞基因如Plk1、Aurora-A、cdk1和Nek2失调，这些基因已知可控制G(2)-M期转换以及有丝分裂的有序进行。