https://scholars.lib.ntu.edu.tw/handle/123456789/516528
標題: | Purpuric drug eruptions induced by EGFR tyrosine kinase inhibitors are associated with IQGAP1-mediated increase in vascular permeability | 作者: | YI-SHUAN SHEEN Lin M.-H. Tzeng W.-C. CHIA-YU CHU |
公開日期: | 2020 | 出版社: | John Wiley and Sons Ltd | 卷: | 250 | 期: | 4 | 起(迄)頁: | 452-463 | 來源出版物: | Journal of Pathology | 摘要: | Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used as a treatment for non-small-cell lung cancer. There have been some reports of EGFR-TKIs being associated with vascular adverse events. We found that EGFR-TKIs decreased the proliferation of HMEC-1s (immortalized human dermal microvascular endothelial cells) and HMVECs (human dermal microvascular endothelial cells), and also inhibited the phosphorylation of EGFR and ERK. We examined the mRNA expression profile of erlotinib-treated HMEC-1s and identified IQ motif containing GTPase activating protein 1 (IQGAP1) as the most consistently up-regulated transcript and protein. IQGAP1 was also overexpressed and co-localized with endothelial cells in the lesional skin. Notably, increased IQGAP1 expression was associated with decreased transendothelial electrical resistance and increased vascular permeability in vitro. Erlotinib treatment enriched the staining of IQGAP1 and reduced the intensities of α-catenin at the sites of cell–cell contact. In conclusion, erlotinib induces adherens junction dysfunction by modulating the expression of IQGAP1 in dermal endothelial cells. ? 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ? 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081359468&doi=10.1002%2fpath.5393&partnerID=40&md5=a29c74116cfd3aa6c9cda5410a33b9d9 https://scholars.lib.ntu.edu.tw/handle/123456789/516528 |
ISSN: | 0022-3417 | DOI: | 10.1002/path.5393 | SDG/關鍵字: | actinin; afatinib; alpha actinin 3; alpha catenin; beta catenin; epidermal growth factor receptor; erlotinib; gefitinib; IQ motif containing guanosine triphosphatase activating protein 1; lmo7 protein; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; nectin 1; protein kinase B; protein tyrosine kinase inhibitor; stress activated protein kinase; unclassified drug; vascular endothelial cadherin; guanosine triphosphatase activating protein; IQ motif containing guanosine triphosphatase activating protein 1; protein kinase inhibitor; quinazoline derivative; adherens junction; Article; blood vessel permeability; cell contact; confocal microscopy; controlled study; dermal microvascular endothelial cell; drug eruption; electric resistance; gene expression; human; human cell; immunofluorescence; in vitro study; keratinocyte; priority journal; protein expression; protein phosphorylation; purpuric rash; real time polymerase chain reaction; RNA interference; upregulation; Western blotting; capillary permeability; drug effect; drug eruption; drug resistance; endothelium cell; genetics; lung tumor; metabolism; mutation; non small cell lung cancer; pathology; proto oncogene; tumor cell line; Capillary Permeability; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drug Eruptions; Drug Resistance, Neoplasm; Endothelial Cells; Genes, erbB-1; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Quinazolines; ras GTPase-Activating Proteins |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。