کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456778 | 1548773 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Oncogenic Function of a KIF5B-MET Fusion Variant in Non-Small Cell Lung Cancer
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
PTKKif5bADCTKITTF-1HGFRET proto-oncogene - RET پروتونوکنAdenocarcinoma - آدنوکارسینوماALK - آلکIHC - ایمونوهیستوشیمیimmunohistochemical - ایمونوهیستوشیمیcomputed tomography - توموگرافی کامپیوتری یا سی تی اسکن یا مقطعنگاری رایانهایRET - حقNSCLC - سرطان ریوی غیر سلول کوچکNon-small cell lung cancer - سرطان غیر سلول کوچک ریهHepatocyte growth factor - عامل رشد هپاتوسیتthyroid transcription factor-1 - فاکتور رونویسی تیروئید 1Anaplastic lymphoma kinase - لنفوم کیناز AnaplasticMET - ملاقات کردTyrosine kinase inhibitor - مهار کننده تیروزین کینازProtein tyrosine kinase - پروتئین تیروزین کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Oncogenic Function of a KIF5B-MET Fusion Variant in Non-Small Cell Lung Cancer Oncogenic Function of a KIF5B-MET Fusion Variant in Non-Small Cell Lung Cancer](/preview/png/8456778.png)
چکیده انگلیسی
A kinesin family member 5b (KIF5B)-MET proto-oncogene, receptor tyrosine kinase (MET) rearrangement was reported in patients with lung adenocarcinoma but its oncogenic function was not fully evaluated. We used one-step reverse transcription-polymerase chain reaction for RNA samples to screen for the KIF5B-MET fusion in 206 lung adenocarcinoma and 28 pulmonary sarcomatoid carcinoma patients. Genomic breakpoints of KIF5B-MET were determined by targeted next-generation sequencing. Soft agar colony formation assays, proliferation assays, and a xenograft mouse model were used to investigate its oncogenic activity. In addition, specific MET inhibitors were administered to evaluate their anti-tumor activities. A KIF5B-MET fusion variant in a patient with a mixed-type adenocarcinoma and sarcomatoid tumor was identified, and another case was found in a pulmonary sarcomatoid carcinoma patient. Both cases carried the same chimeric gene, a fusion between exons 1-24 of KIF5B and exons 15-21 of MET. KIF5B-MET-overexpressing cells exhibited significantly increased proliferation and colony-forming ability. Xenograft tumors harboring the fusion gene demonstrated significantly elevated tumor growth. Ectopic expression of the fusion gene stimulated the phosphorylation of KIF5B-MET as well as downstream STAT3, AKT, and ERK1/2 signaling pathways. The MET inhibitors significantly repressed cell proliferation; phosphorylation of downstream STAT3, AKT, and ERK1/2; and xenograft tumorigenicity. In conclusion, the KIF5B-MET variant was demonstrated to have an oncogenic function in cancer cells. These findings have immediate clinical implications for the targeted therapy of subgroups of non-small cell lung cancer patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 20, Issue 8, August 2018, Pages 838-847
Journal: Neoplasia - Volume 20, Issue 8, August 2018, Pages 838-847
نویسندگان
Chien-Hung Gow, Yi-Nan Liu, Huei-Ying Li, Min-Shu Hsieh, Shih-Han Chang, Sheng-Ching Luo, Tzu-Hsiu Tsai, Pei-Lung Chen, Meng-Feng Tsai, Jin-Yuan Shih,