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Noninvasive imaging and quantification of epidermal growth factor receptor kinase activation in vivo

文献类型： 外文期刊

作者： Li, Wenrong 1 ; Li, Fang 1 ; Huang, Qian 1 ; Frederick, Barbara 1 ; Bao, Shideng 1 ; Li, Chuan-Yuan 1 ;

作者机构： 1.Univ Colorado, Hlth Sci Ctr, Dept Radiat Oncol, Aurora, CO 80010 USA

2.Univ Colorado, Hlth Sci Ctr, Dept Neurosurg, Aurora, CO 80010 USA

3.Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO 80010 USA

4.Xinjiang Acad Anim Sci, Urumqi, Xinjiang, Peoples R China

5.Shanghai Jiao Tong Univ, Peoples Hosp 1, Shanghai 200030, Peoples R China

期刊名称：CANCER RESEARCH （ 影响因子：12.701； 五年影响因子：12.843 ）

ISSN： 0008-5472

年卷期： 2008 年 68 卷 13 期

页码：

收录情况： SCI

摘要： Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) critical in tumor growth and a major target for anticancer drug development. However, thus far, there is no effective system to monitor its activities in vivo. Here, we report a novel approach to monitor EGFR activation based on the bifragment luciferase reconstitution system. The EGFR receptor and its interacting partner proteins (EGFR, growth factor receptor binding protein 2, and Src homology 2 domain-containing) were fused to NH2 terminal and COOH terminal fragments of the firefly luciferase. After establishing tumor xenograft from cells transduced with the reporter genes, we show that the activation of EGFR and its downstream factors could be quantified through optical imaging of reconstituted luciferase. Changes in EGFR activation could be visualized after radiotherapy or EGFR inhibitor treatment. Rapid and sustained radiation-induced EGFR activation and inhibitor-mediated signal suppression were observed in the same xenograft tumors over a period of weeks. Our data therefore suggest a new methodology where activities of RTKs can be imaged and quantified optically in mice. This approach should be generally applicable to study biological regulation of RTK, as well as to develop and evaluate novel RTK-targeted therapeutics.

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