Cis-acting element involved in the repression of the HER-2/neu oncogene expression by EBNA-1
碩士 === 國防醫學院 === 生物化學研究所 === 86 === The overexpression and/or amplification of the HER-2/neu protooncogene were frequently demonstrated in a wide variety of human cancer. It was shown to be correlated with the progression of tumor metastasis and chemoresistance. Therefore, Repression of HER-2/neu ge...
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| Format: | Others |
| Language: | zh-TW |
| Published: |
1998
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| Online Access: | http://ndltd.ncl.edu.tw/handle/72834584604061769669 |
| Summary: | 碩士 === 國防醫學院 === 生物化學研究所 === 86 === The overexpression and/or amplification of the HER-2/neu protooncogene were frequently demonstrated in a wide variety of human cancer. It was shown to be correlated with the progression of tumor metastasis and chemoresistance. Therefore, Repression of HER-2/neu gene expression will be the potent at target for gene therapy focused on HER-2/neu overexpression cancer cells. Our previous studies showed that the Epstein-Barr virus nuclear antigen-1 (EBNA-1) suppresses the HER-2/neu oncogene expression at the transcriptional level. The EBNA-1 was also found to be able to downregulate the endogenous production of p185HER-2/neu. These data suggest that the EBNA-1 may act as a transforming repressor of HER-2/neu oncogene. However, the detail repression mechanism was not completely understood. The purpose of this study is to investigate how the HER-2/neu promoter is regulated by EBNA-1. Using deletion mutation approach, we found that the StuI-XhoI region on the HER-2/neu promoter seems to be responsible for the repression of the HER-2/neu gene expression. Electrophoresis mobility shift (EMSA) showed that a shifted band was observed in control SKOV-3 cells but not in EBNA-1 transfected SKOV-3 cells. It suggested that there may be a positive regulatory transcription factor on the HER-2/neu promoter was replaced EBNA-1 protein and repressed HER-2/neu oncogene transcription.
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