High-risk human papillomavirus type 16 E7 oncogene associates with Cdc25A over-expression in oral squamous cell carcinoma
High-risk human papillomavirus type 16 E7 oncogene associates with Cdc25A over-expression in oral squamous cell carcinoma
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DOI：
10.1007/s00428-006-0327-x
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发表时间：
2007-01-01
期刊：
影响因子：
3.5
通讯作者：
Kuniyasu, Hiroki
中科院分区：
文献类型：
--
作者：
Bhawal, Ujjal Kumar;Sugiyama, Masaru;Kuniyasu, Hiroki
表达高危人乳头瘤病毒(HPV)E7蛋白的细胞在DNA损伤后表现出检查点控制受损，并表现出较高的突变率。抑制HPVE7的表达会导致视网膜母细胞瘤蛋白的低磷酸化积累和CDC25A基因的抑制。目前尚无研究阐明CDC25A在口腔癌发生发展中的作用。应用免疫组织化学、Western blotting、聚合酶链式反应(PCR)和逆转录-聚合酶链式反应(RT-PCR)对不同组织学亚型口腔癌组织中CDC25A蛋白的表达和HPV的表达进行了研究。CDC25A蛋白在癌组织中主要定位于细胞核，在54%的原发肿瘤中呈高表达。HPV-16E7在非肿瘤性口腔组织中未见表达，而在22例口腔癌中有8例(36%)表达。我们发现CDC25A的过度表达与HPV-16E7阳性的癌有显著的相关性。CDc25A过表达与肿瘤大小、TNM分期呈显著正相关。本研究提示，CDC25A可能是口腔肿瘤发生发展过程中的重要介质，HPV-16E7可能是病毒癌基因参与口腔癌发生的敏感指标。
Cells expressing high-risk human papillomavirus (HPV) E7 protein display impaired checkpoint control after DNA damage and exhibit elevated rates of mutagenesis. Repression of HPV E7 expression results in the subsequent accumulation of hypophosphorylated retinoblastoma protein and repression of the Cdc25A genes. No study has been conducted to elucidate the role of Cdc25A in the development and progression of human oral carcinomas. To confirm Cdc25A protein expression together with HPV, immunohistochemistry, Western blotting, polymerase chain reaction (PCR), and reverse transcriptase (RT)-PCR were performed using various histological subtypes of oral carcinomas. Cdc25A protein was localized predominantly in the cell nuclei in carcinomas, and high expression was found in 54% of primary tumors. HPV-16 E7 was not found in non-neoplastic oral tissues, whereas it was observed in eight (36%) of 22 oral carcinomas. We found a significant correlation between Cdc25A over-expression and HPV-16 E7 positive carcinomas. There was a strong positive correlation between Cdc25A over-expression and tumor size and TNM stage. This study suggests that Cdc25A is likely to be an important mediator in the progression of oral tumors, and HPV-16 E7 may be a sensitive indicator of the involvement of viral oncogenes in oral carcinogenesis.