癌細胞增生中致癌蛋白EGFR在細胞核內功能之探討

CMUR > College of Medicine > Graduate Institute of Medical Science > Research reports > Item 310903500/25453

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Title:	癌細胞增生中致癌蛋白EGFR在細胞核內功能之探討 The Nuclear Function of EGFR Receptor in Cancer Cell Proliferation
Authors:	余永倫
Contributors:	中國醫藥大學醫學研究所
Keywords:	核內EGFR;增生細胞核抗原;磷酸化;nuclear EGFR;PCNA;phosphorylation
Date:	2009-07
Issue Date:	2010-09-02 17:49:44 (UTC+8)
Abstract:	致癌蛋白 EGFR 被發現存在細胞核內已經超過十年了。然而我們對於核內EGFR 在癌細胞中的生理功能以及訊息傳遞路徑的瞭解才剛起步。在過去的研究中發現，當快速增生的肝臟其肝細胞不斷地增生時常緊密伴隨著核內EGFR 表現的增加。同時在許多癌症檢體中包括乳癌檢體常常也發現有核內EGFR 過量表現，且最近已經被證實核內 EGFR 可以被用來當作癌症病患的癒後分子標記。經由我們最新的研究發現，增生細胞核抗原(PCNA) 能被核內EGFR 在其酪氨酸211(Tyr 211)的位置磷酸化，此磷酸化能強化其蛋白的穩定性。除此之外，我們推測EGFR 能在核內與許多細胞核內蛋白形成功能性的複合體。所以在這次我們所提的計畫中，第一個目的是要鑑定與分析新穎的核內EGFR 目標蛋白與其複合體。此外，我們第二個目的將進一步探討被核內EGFR 在Tyr 211 位置所磷酸化的PCNA 在癌細胞增生過程中的重要性。最後，第三個目的我們將專注於研究核內EGFR 它的轉譯後修飾特別是磷酸化在細胞核內的角色與功能。這個計畫的執行不但可以讓我們更瞭解核內EGFR 的功能，而且更有助於未來成功發展出抑制細胞核內 EGFR 訊息傳遞的新穎癌症治療方法。 Nuclear existence of epidermal growth factor receptor (EGFR) has been documented for more than a decade. However, our understanding of the physiological contribution of the nuclear EGFR signaling to the biology in cancer cells is just about to emerge. In regenerating liver, increased nuclear EGFR expression is closely associated with active hepatocyte proliferation. In cancer, nuclear expression of EGFR is frequently associated with multiple tumor types, including breast cancer, and has been shown to be a poor prognosis tumor marker for cancer patients. We recently demonstrated that the proliferating cell nuclear antigen (PCNA) protein is subject to tyrosine phosphorylation at tyrosine 211 (Tyr 211) by nuclear EGFR and the phosphorylation enhances PCNA stability. In addition, EGFR appears to form functional complexes with multiple nuclear proteins. In this proposal, we aim to characterize the interactome of nuclear EGFR and identify its novel nuclear partners (Aim1). Furthermore, we will extend our study to explore the importance of the nuclear EGFR mediated Tyr 211 phosphorylation of PCNA in cancer cell proliferation (Aim2). Finally, we will study the nuclear EGFR for its post-translational modification in particular tyrosine phosphorylation, and the associated functions in the nucleus (Aim3). The proposed work will greatly extend our knowledge on the nuclear function of EGFR, which may facilitate the future success to develop novel therapies that target the nuclear EGFR signaling pathway in cancer.
Appears in Collections:	[Graduate Institute of Medical Science] Research reports

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