Oxidative stress in HPV-driven viral carcinogenesis: redox proteomics analysis of HPV-16 dysplastic and neoplastic tissues.
Oxidative stress in HPV-driven viral carcinogenesis: redox proteomics analysis of HPV-16 dysplastic and neoplastic tissues.
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DOI：
10.1371/journal.pone.0034366
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Perluigi M
中科院分区：
文献类型：
--
作者：
De Marco F;Bucaj E;Foppoli C;Fiorini A;Blarzino C;Filipi K;Giorgi A;Schininà ME;Di Domenico F;Coccia R;Butterfield DA;Perluigi M
高危型人乳头瘤病毒（HR-HPV）生殖器感染虽然被认为是宫颈癌的主要致病因素，但其本身不足以诱发肿瘤的发生。氧化应激 (OS) 是 HPV 引发的癌变的一个有趣且尚未充分探索的候选因素。为了深入了解 OS 在宫颈癌中的作用，从浸润性鳞状宫颈癌患者、高度不典型增生 HPV 病变患者和无 HPV 病变临床证据的患者中收集了 HPV-16 阳性组织。病毒学表征后，研究了参与氧化还原状态调节的蛋白质的调节。 ERp57 和 GST 在发育异常和肿瘤组织中急剧升高。 TrxR2 在发育不良样本中达到峰值，而 iNOS 在发育不良和肿瘤样本中逐渐减少。通过氧化还原蛋白质组学方法，发现发育不良样品中的五种蛋白质的羰基水平相对于对照有所增加，即：细胞角蛋白 6、肌动蛋白、cornulin、视网膜脱氢酶和 GAPDH。在癌样本中，肽基脯氨酰顺反异构酶 A、ERp57、丝氨酸蛋白酶抑制剂 B3、膜联蛋白 2 和 GAPDH 的氧化程度低于发育不良组织。 HPV16 肿瘤进展似乎与氧化环境增加有关。在发育不良组织中，参与细胞形态发生和终末分化的DNA和蛋白质的氧化修饰可能为肿瘤进展提供条件。相反，癌症组织似乎对氧化损伤的控制得到了改善，如关键解毒/促生存蛋白上羰基加合物的选择性减少所示。
Genital infection by high risk Human Papillomavirus (HR-HPV), although recognized as the main etio-pathogenetic factor of cervical cancer, is not per se sufficient to induce tumour development. Oxidative stress (OS) represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. To gain insight into the role of OS in cervical cancer, HPV-16 positive tissues were collected from patients with invasive squamous cervical carcinoma, from patients with High Grade dysplastic HPV lesions and from patients with no clinical evidence of HPV lesions. After virological characterization, modulation of proteins involved in the redox status regulation was investigated. ERp57 and GST were sharply elevated in dysplastic and neoplastic tissues. TrxR2 peaked in dysplastic samples while iNOS was progressively reduced in dysplastic and neoplastic samples. By redox proteomic approach, five proteins were found to have increased levels of carbonyls in dysplastic samples respect to controls namely: cytokeratin 6, actin, cornulin, retinal dehydrogenase and GAPDH. In carcinoma samples the peptidyl-prolyl cis-trans isomerase A, ERp57, serpin B3, Annexin 2 and GAPDH were found less oxidized than in dysplastic tissues. HPV16 neoplastic progression seems associated with increased oxidant environment. In dysplastic tissues the oxidative modification of DNA and proteins involved in cell morphogenesis and terminal differentiation may provide the conditions for the neoplastic progression. Conversely cancer tissues seem to attain an improved control on oxidative damage as shown by the selective reduction of carbonyl adducts on key detoxifying/pro-survival proteins.
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影响因子：
7.4
作者：
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通讯作者：
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Dynan, William S.
影响因子：
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作者：
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