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AXL is crucial for E1A-enhanced therapeutic efficiency of EGFR tyrosine kinase inhibitors through NFI in breast cancer
Environmental Toxicology ( IF 4.4 ) Pub Date : 2021-03-18 , DOI: 10.1002/tox.23125
Chih-Ming Su, Tung-Wei Hsu, Shian-Ying Sung, Ming-Te Huang, Kuan-Chou Chen, Chih-Yang Huang, Chien Yi Chiang, Yen-Hao Su, Hsin-An Chen, Po-Hsiang Liao

AXL which is a chemosensitizer protein for breast cancer cells in response to epidermal growth factor receptor-tyrosine kinase inhibitor and suppresses tumor growth. The clinical information show nuclear factor I (NFI)-C and NFI-X expression correlate with AXL expression in breast cancer patients. Following, we establish serial deletions of AXL promoter to identify regions required for Adenovirus-5 early region 1A (E1A)-mediated AXL suppression. All of the NFI family members were extensively studied for their expression and functions in regulating AXL. Moreover, E1A post-transcriptionally downregulates AXL expression through NFI. NFI-C and NFI-X, not NFI-A and NFI-B, resulting in cell death in response to EGFR-TKI. Our finding suggests that NFI-C and NFI-X are crucial regulators for AXL and significantly correlated with poor survival of breast cancer patients.

中文翻译:

AXL 对于通过 NFI 在乳腺癌中通过 E1A 增强 EGFR 酪氨酸激酶抑制剂的治疗效率至关重要

AXL 是乳腺癌细胞对表皮生长因子受体酪氨酸激酶抑制剂的一种化学增敏剂蛋白,可抑制肿瘤生长。临床资料显示核因子 I (NFI)-C 和 NFI-X 表达与乳腺癌患者的 AXL 表达相关。接下来,我们建立了 AXL 启动子的连续缺失,以识别 Adenovirus-5 早期区域 1A (E1A) 介导的 AXL 抑制所需的区域。广泛研究了所有 NFI 家族成员在调节 AXL 中的表达和功能。此外,E1A 通过 NFI 转录后下调 AXL 表达。NFI-C 和 NFI-X,而不是 NFI-A 和 NFI-B,导致细胞死亡以响应 EGFR-TKI。
更新日期:2021-03-18
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