Activation of DNA damage repair factors in HPV positive oropharyngeal cancers
Activation of DNA damage repair factors in HPV positive oropharyngeal cancers
复制标题
DOI：
10.1016/j.virol.2020.05.003
复制
发表时间：
2020-08-01
期刊：
影响因子：
3.7
通讯作者：
Laimins, Laimonis A.
中科院分区：
文献类型：
--
作者：
Kono, Takeyuki;Hoover, Paul;Laimins, Laimonis A.
调节人乳头瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）的病毒发病机制尚不清楚。在子宫颈，DNA损伤修复途径的激活对病毒复制至关重要，但对其在OPSCC中的作用知之甚少。APOBEC因子已被证明在OPSCC中增加，但其意义尚不清楚。因此，我们检测了hpv诱导的OPSCC中DNA损伤和APOBEC因子的激活。我们的研究表明，与hpv阴性相比，hpv阳性样本中pCHK1、FANCD2、BRCA1、RAD51、pSMC1和γ H2AX灶的水平显著升高，而ATM效应激酶pCHK2没有升高。在OPSCC细胞系中检测蛋白质水平时也观察到类似的差异。相比之下，在hpv阳性和阴性的OPSCC中，APOBEC3B和3A的水平相似。我们的研究提示ATR通路成员和FANCD2可能在hpv诱导的OPSCC中起重要作用。
The mechanisms regulating viral pathogenesis of human papillomavirus (HPV) associated oropharyngeal squamous cell cancers (OPSCC) are not well understood. In the cervix, activation of DNA damage repair pathways is critical for viral replication but little is known about their role in OPSCC. APOBEC factors have been shown to be increased in OPSCC but the significance of this is unclear. We therefore examined activation of DNA damage and APOBEC factors in HPV-induced OPSCC. Our studies show significantly increased levels of pCHK1, FANCD2, BRCA1, RAD51, pSMC1 and gamma H2AX foci in HPV-positive samples as compared to HPV-negative while the ATM effector kinase, pCHK2, was not increased. Similar differences were observed when the levels of proteins were examined in OPSCC cell lines. In contrast, the levels of APOBEC3B and 3A were found to be similar in both HPV-positive and -negative OPSCC. Our studies suggest members of ATR pathway and FANCD2 may be important in HPV-induced OPSCC.