Nuclear Translocation of Epidermal Growth Factor Receptor by Akt-dependent Phosphorylation Enhances Breast Cancer-resistant Protein Expression in Gefitinib-resistant Cells

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/16660

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/16660

题名:	Nuclear Translocation of Epidermal Growth Factor Receptor by Akt-dependent Phosphorylation Enhances Breast Cancer-resistant Protein Expression in Gefitinib-resistant Cells
作者:	黃偉謙;Huang, Wei-Chien;李龍緣;Li, Long-Yuan;Chang, Wei-Chao;Chang, Wen-Chang;Chen, Andy Jer-En;Tsai, Chang-Hai
贡献者:	生物科技學系
关键词:	Drug Resistance;Gene Regulation, Nuclear Translocation;Protein Phosphorylation;Receptor-tyrosine Kinase;Akt;BCRP/ABCG2;Gefitinib, Nuclear EGFR
日期:	2011-06
上传时间:	2012-11-23 17:15:35 (UTC+8)
摘要:	Epidermal growth factor receptor (EGFR), an aberrantly overexpressed or activated receptor-tyrosine kinase in many cancers, plays a pivotal role in cancer progression and has been an attractive target for cancer therapy. Gefitinib and erlotinib, two EGFR-tyrosine kinase inhibitors, have been approved for non-small cell lung cancer. However, durable clinical efficacy of these EGFR inhibitors is severely limited by the emergence of acquired resistance. For example, the expression of breast cancer-resistant protein (BCRP/ABCG2) has been shown to confer acquired resistance of wild-type EGFR (wtEGFR)-expressing cancer cells to gefitinib. However, the underlying molecular mechanisms still remain unclear. Here, we show that wtEGFR expression is elevated in the nucleus of acquired gefitinib-resistant cancer cells. Moreover, nuclear translocation of EGFR requires phosphorylation at Ser-229 by Akt. In the nucleus, EGFR then targets the proximal promoter of BCRP/ABCG2 and thereby enhances its gene transcription. The nuclear EGFR-mediated BCRP/ABCG2 expression may contribute at least in part to the acquired resistance of wtEGFR-expressing cancer cells to gefitinib. Our findings shed light on the role of nuclear EGFR in the sensitivity of wtEGFR-expressing cancer cells to EGFR tyrosine kinase inhibitors and also deciphered a putative molecular mechanism contributing to gefitinib resistance through BCRP/ABCG2 expression.
關聯:	JOURNAL OF BIOLOGICAL CHEMISTRY
显示于类别:	[生物科技學系] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	393	检视/开启

在ASIAIR中所有的数据项都受到原著作权保护.

数据加载中.....