Eps8 (EGF receptor pathway substrate No.8)是一個常見的EGF receptor及Src的共同受質。它會參與在EGF所調控的細胞分裂及腫瘤生成當中。此外，當減弱Eps8表達時不僅會減慢子宮頸癌細胞-HeLa及SiHa的細胞生長速率，而且還會增加細胞對於化療藥物cisplatin及paclitaxel的敏感性。此外，隨著Eps8 減弱，腫瘤抑制蛋白p53的表現量有上升的情形；而Src及Akt的活性則會減少。在先前實驗室的研究發現，在大腸直腸癌細胞-HCT116也同樣發現當Eps8減弱時， p53表現量會提升，造成細胞週期停滯及對於cisplatin的敏感性增加。因此為了測試p53在Eps8所調控的對於cisplatin耐藥性的重要性，我們利用wild-type HCT116細胞和p53敲除HCT116細胞來觀察它們對於藥物的敏感性和DNA修復能力。在HCT116細胞中Eps8 減弱及p53敲除會減少細胞的存活率和DNA修復能力。有趣的是，在將Eps8外送進入以cisplatin處理的p53 敲除HCT116細胞後會部分回復DNA修復能力及增加細胞存活率。顯示Eps8所參與的的細胞存活和DNA修復可能是經由p53 independent的途徑。藉由centrifugation fractionation，我們發現當Eps8表現量減少可能會抑制p53及Ku70在HeLa細胞中入核的能力。此外，在減少Ku70表現時會增加HeLa細胞對於cisplatin的敏感性，且會減少DNA修復能力，我們認為經由p53及Ku70，Eps8可能會調控癌細胞的化學敏感性。

Eps8 (EGF receptor pathway substrate No.8) is a common substrate of EGF receptor and Src. It participates in EGF-mediated mitogenesis and tumorigenesis. Interestingly, attenuation of Eps8 reduces not only cell proliferation of cervical cancer cells --HeLa and SiHa, but also renders them to be more sensitive to cisplatin and paclitaxel. Besides, accompanying with Eps8 knockdown , we observed tumor suppressor protein p53 is up-regulated while the activity of Src and Akt is reduced. In HCT116 colon cancer cell, we also observed when Eps8 knockdown also elevates p53, causes cell cycle arrest, and increases sensitivity to cisplatin. To test the importance of p53 in Eps8-mediated drug resistance against cisplatin, we utilized wild-type HCT116 cell and p53 null HCT116 cells to examine their drug sensitivity and DNA repairing ability. Both Eps8-attenuated cells and p53-null cells, exhibits reduced cell survival and DNA repairing ability in HCT116 cell. Interestingly, ectopic Eps8 partly restored the DNA repair ability and increased cell survival of cisplatin-treated p53 null HCT116 cells . This suggested that Eps8-mediated cell survival and DNA repair might be through p53 independent pathway. By centrifugation fractionation. We found that Eps8 knockdown inhibited nuclear translocation of both p53 and Ku70in HeLa cells. Since, Ku70 attenuation increased the sensitivity of HeLa cell to the toxicity of cisplatin and decreased DNA repairing ability, we conclude that, via p53 and Ku70, Eps8 might modulate the chemosensitivity of cancer cells.

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