Aberrant Expression of Notch1 in Cervical Cancer

摘要

OBJECTIVE To investigate the putative role of the Notchi receptor in cervical cancer carcinogenesis and progression. METHODS The expression of the Notchi protein was analyzed by a Western-blotting approach in 40 cervical cancer and 30 normal cervical tissues. Some tissues were examined using RT-PCR to determine mRNA levels. Celluar localization of the Notchi protein in the paraffin-embedded cervical tissues was also analyzed by immunohistochemistry. RESULTS The Notchi protein was detected in all 30 normal cervical tissues. In contrast, only 6 samples of 40 cervical cancer tissues showed Notchi expression. The level of the Notchi protein expression was significantly lower in cervical cancer tissues than that in normal tissue samples. In agreement with these observations, levels of Notchi mRNA were found to be substantially down-regulated in cervical cancer tissues. In the immunohistochemistry staining assay, the Notchi protein was shown to localize predominantly in the cytoplasm and nucleoli of the normal cervical squamous epithelium of the cervix, but no staining was observed in the cervical cancer cells. Notchi expression was observed to correlate with the clinical disease stage, but there were no correlations with age, tumor size, grade or lymph node metastasis (P > 0.05). The levels of Notchi protein expression were significantly higher in early stages (Ⅰ～Ⅱa, 66.7%) compared to those in the advanced stages (Ⅱb～Ⅳ,12.6%)(P=0.001). CONCLUSION Notchi may play a role as a tumor suppressor in cervical tumorigenesis. Determination of Notchi expression may be helpful for preoperative diagnosis and accuracy of staging. But its clinical use for cervical cancer requires further investigation.