Induction of Apoptosis in HER-2-overexpressing Cancer Cells by siRNA against HER-2

• Main Authors: Hsin-Fang Lee, 李幸芳
• Other Authors: 王萬波
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/63874208939166746277

碩士 === 國立臺灣大學 === 微生物學研究所 === 92 === HER-2 gene is a proto-oncogene which belongs to the epidermal growth factor receptor family. It is overexpressed in many human cancers, including breast, lung, ovary, pancreas, gastric, and oral cancers. HER-2-overexpressing cancer cells usually have higher potential to proliferate, metastasize, induce angiogenesis, and resist chemotherapeutic agents. Inhibition of HER-2 can lead to suppression of the tumorigenicity of HER-2-overexpressing cancer cells. Therefore HER-2/neu gene is a suitable target for cancer treatment. To search for new ways to treat HER-2-overexpressing cancers, I have used small interfering RNA (siRNA) strategy to inhibit HER-2 expression in HER-2-overexpressing cancer cells. Three pSUPER plasmids which express different HER-2 siRNA were constructed. These plasmids were tested for their ability to inhibit HER-2 expression and to induce apoptosis of HER-2-overexpressing cancer cells. I have found that one of these siRNA constructs, HER-2-siRNA-3, can efficiently inhibit HER-2 expression in HER-2–overexpressing cancer cells. Moreover, this siRNA construct was shown to be able to specifically induce apoptosis in HER-2-overexpressing cancer cells but not in HER-2 low-expressing cancer cells. I also constructed a recombinant adenovirus, rAd-siHER-2-3, that can expresses HER-2-siRNA-3. rAd-siHER-2-3 infection was shown to be able to inhibit HER-2 expression and induce apoptosis in HER-2-overexpressing cancer cells. Taken together, these data suggest that HER2-siRNA-3 may be developed as a therapeutic agent against HER-2-overexpressing cancers.