| http://purl.uniprot.org/citations/21487020 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21487020 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21487020 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.240796"xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.240796"xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chen C.H."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chen C.H."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chen Y.J."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chen Y.J."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Tsai C.H."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Tsai C.H."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chang W.C."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chang W.C."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Li L.Y."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Li L.Y."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Hung M.C."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Hung M.C."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Wang Y.N."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Wang Y.N."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Huang W.P."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Huang W.P."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chang W.C.'"xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Chang W.C.'"xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Huang W.C."xsd:string |
| http://purl.uniprot.org/citations/21487020 | http://purl.uniprot.org/core/author | "Huang W.C."xsd:string |