Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/23753
標題: Cdk5於表皮生長因子受體蛋白參與之攝護腺癌細胞增生中所扮演之角色
The role of Cdk5 on EGFR-dependent proliferation of prostate cancer cells
作者: 彭裕婷
Peng, Yu-Ting
關鍵字: EGFR
表皮生長因子受體蛋白
Cdk5
prostate cancer
cell proliferation
Cdk5
攝護腺癌
細胞增生
出版社: 生命科學系所
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摘要: 攝護腺癌(prostate cancer)在美國男性癌症死亡率中長期以來都佔居第二名,僅次於肺癌,臺灣地區攝護腺癌死亡率雖然僅排名第七位,但是死亡人數有逐年上升的趨勢,因此,科學家正積極研究攝護腺癌的調控機制。表皮生長因子受體蛋白 (Epidermal growth factor receptor, EGFR)為ErbB家族的成員,在其他癌症已經被發現參與重要調控,而在攝護腺癌的研究中,EGFR也會調控攝護腺癌細胞增生。根據我們實驗室2007年發表的文獻指出,同為ErbB家族成員的Her2蛋白會透過cyclin-dependent kinase 5 (Cdk5)和signal transducer and activator of transcription 3 (STAT3)來調控甲狀腺癌細胞的增生,因此我們假設,在攝護腺癌細胞中,EGFR會藉由Cdk5和STAT3來調控攝護腺癌細胞的生長。首先,我們先觀察EGFR的活化與否對攝護腺癌細胞生長的影響,處理EGF刺激EGFR活化或是處理EGFR的抑制劑Iressa,結果觀察到確實與前人所做的結果一樣,EGF刺激攝護腺癌細胞生長,Iressa抑制攝護腺癌細胞生長。我們也關心EGFR和Cdk5兩者的關係,改變EGFR的活性可以影響EGFR和Cdk5的交互作用,而且改變EGFR的活性會造成Cdk5-Y15表現量受到影響,利用離體磷酸酶活性分析 (in vitro kinase assay)EGFR是否會磷酸化Cdk5,結果可知EGFR有磷酸化Cdk5的情形,EGF也會使Cdk5活性增加。為了探討EGFR活化後是否透過Cdk5調控攝護腺癌細胞生長,利用siCdk5或是過度表現Cdk5 mutant (Y15F),阻斷Cdk5的表現,發現knock down Cdk5之後即使給予EGF的刺激,細胞生長有受到抑制的情形,過度表現Cdk5-Y15F也會抑制攝護腺癌細胞生長。此外,我們也觀察到EGFR的活性會調控STAT3-Ser727 (STAT3-S727)磷酸化。根據目前本篇論文的研究,EGFR會透過Cdk5調控攝護腺癌細胞生長,特別是透過磷酸化Cdk5-Y15,期望未來EGFR/Cdk5/STAT3這條訊息傳遞鏈對攝護腺癌增生的調控機制能夠更明確。
Epidermal growth factor receptor (EGFR) plays an important role on various cancers. In previous study, EGFR has been found to modulate prostate cancer cell proliferation. Iressa, a specific inhibitor of EGFR, was reported to decrease prostate cancer cell proliferation. Our previous results indicated that Her2 could regulate thyroid cancer cell proliferation through cyclin-dependent kinase 5 (Cdk5) and signal transducer and activator of transcription 3 (STAT3). In the present study, we found that EGFR activation could induce tyrosine 15 (Y15) phosphorylation of Cdk5 and its activation. In addition, the interaction of EGFR and Cdk5 was also increased by EGFR activation. Knock down Cdk5 even treating EGF inhibited proliferation of prostate cancer cells. And overexpression of Cdk5 mutant (Cdk5-Y15F) inhibited proliferation of prostate cancer cells. On the other hand, Ser727 (S727) of STAT3 was phosphorylated after EGFR activation and the interaction of Cdk5 and STAT3 was increased. Iressa treatment in prostate cancer cells could diminish the activation of either EGFR or Cdk5/STAT3. Taken together, EGFR might support cell proliferation of prostate cancer through regulating Cdk5, especially Cdk5-Y15 phosphorylation.
URI: http://hdl.handle.net/11455/23753
其他識別: U0005-2007201113012400
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