HER-2 siRNA造成HER-2大量表現癌細胞凋亡之研究

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

李幸芳(Hsin-Fang Lee)

指導教授 ： 王萬波

國立臺灣大學/醫學院/微生物學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.01750

摘要

HER-2屬於表皮生長因子接受器家族(epidermal growth factor receptor family；EGF receptor family)的一員。HER-2基因在許多人類癌症中時常有放大(amplification)或過度表現(overexpression)的現象，目前已知HER-2可以傳遞數個不同的信號路徑，這些路徑導致HER-2具有強大的致癌能力，因此，HER-2被認為是治療癌症的標的之一。
我們實驗室設計了HER-2的siRNA，可以有效抑制HER-2的表現，並在數株HER-2-overexpressing細胞中，發現可以導致細胞走向凋亡，而對於HER-2 low-expressing細胞無影響，因此，此siRNA具有用於治療HER-2-overexpressing癌症的潛力。

關鍵字

表皮生長因子接受器 ； 小干擾核醣核酸

並列摘要

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.

並列關鍵字

HER-2 ； siRNA

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