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Down-Modulation of Notch1 Expression in Cervical Cancer Is Associated with HPV-Induced Carcinogenesis

Down-Modulation of Notch1 Expression in Cervical Cancer Is Associated with HPV-Induced Carcinogenesis
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摘要 OBJECTIVE Notch1 signaling has been implicated intumorigenesis. The purpose of this study was to investigate theputative role of the Notch1 receptor in carcinogenesis and in theprogression of the cervical cancer. Since human papillomavirus(HPV) is a causative agent in cervical carcinoma, the interactionbetween Notch1 and HPV infection was examined.METHODS Forty cervical cancer samples and 30 normalcervical tissue specimens were examined using Western blot andRT-PCR to detect Notch1 protein and mRNA levels. HPV16 DNAwas examined in all samples using PCR.RESULTS The level of Notch1 protein expression wassignificantly lower in cervical cancer tissue than in normal tissue.Levels of Notch1 mRNA were found to be substantially downregulatedin cancer tissue. Notch1 protein expression levelswere significantly higher in carcinomas without HPV DNAthan that in carcinomas with HPV infection (55.5% vs. 3.3%, P <0.05). Down-modulation of Notch1 mRNA levels in carcinomawas demonstrated to be associated with HPVE6 transcription.Moreover, levels of Notch1 expression were shown to besignificantly higher in early stage disease than in advanced stagedisease (P = 0.001).CONCLUSION Down-modulation of Notch1 expressionprobably plays an important role in the late stages of HPVinducedcervical cancer. OBJECTIVE Notch1 signaling has been implicated in tumorigenesis. The purpose of this study was to investigate the putative role of the Notch1 receptor in carcinogenesis and in the progression of the cervical cancer. Since human papillomavirus (HPV) is a causative agent in cervical carcinoma, the interaction between Notch1 and HPV infection was examined. METHODS Forty cervical cancer samples and 30 normal cervical tissue specimens were examined using Western blot and RT-PCR to detect Notch1 protein and mRNA levels. HPV16 DNA was examined in all samples using PCR. RESULTS The level of Notch1 protein expression was significantly lower in cervical cancer tissue than in normal tissue. Levels of Notch1 mRNA were found to be substantially downregulated in cancer tissue. Notch1 protein expression levels were significantly higher in carcinomas without HPV DNA than that in carcinomas with HPV infection (55.5% vs. 3.3%, P 〈 0.05). Down-modulation of Notch1 mRNA levels in carcinoma was demonstrated to be associated with HPVE6 transcription. Moreover, levels of Notch1 expression were shown to be significantly higher in early stage disease than in advanced stage disease (P = 0.001). CONCLUSION Down-modulation of Notch1 expression probably plays an important role in the late stages of HPV- induced cervical cancer.
出处 《Clinical Oncology and Cancer Research》 CAS CSCD 2009年第6期401-405,共5页 临床肿瘤与癌症研究(英文版)
关键词 cervical cancer NOTCH1 human papillomavirus (HPV). 人乳头瘤病毒16型 子宫颈癌 癌变 诱发 调制 mRNA水平 乳头状瘤病毒 PCR检测
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参考文献10

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