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

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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. The purpose of this study was to investigate the role of the Notch1 receptor in carcinogenesis and in theprogression of the cervical cancer. Since the purpose of this study was to investigate the role of the Notch1 receptor in carcinogenesis and in theprogression of the cervical cancer. HPV infection was examined. METHODS Forty cervical cancer samples and 30 normalcervical tissue specimens were examined using Western blot and RT-PCR to detect Notchl protein and mRNA levels. HPV16 DNA was 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 downregulated in 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 carcinoma was demonstrated to be associate d with HPVE6 transcription. More over, levels of Notch1 expression were shown to be moreificly higher in early stage disease than in advanced stagedisease (P = 0.001) .CONCLUSION Down-modulation of Notch1 expression probably plays an important role in the late stages of HPV induction of vulvar cancer.
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