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

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. HPV16DNA 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 down-regulated 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.