PMID- 28906590 OWN - NLM STAT- MEDLINE DCOM- 20180320 LR - 20221207 IS - 1759-7714 (Electronic) IS - 1759-7706 (Print) IS - 1759-7706 (Linking) VI - 8 IP - 6 DP - 2017 Nov TI - FGF19 genetic amplification as a potential therapeutic target in lung squamous cell carcinomas. PG - 655-665 LID - 10.1111/1759-7714.12504 [doi] AB - BACKGROUND: Although FGF19 gene aberrations are associated with carcinogenesis and progression in human cancers, the roles of FGF19 genetic amplification and expression in Chinese patients with lung squamous cell carcinoma (LSCC) and FGF19 amplification as a potential therapeutic target for LSCC are not well understood. METHODS: Fluorescence in situ hybridization analysis and quantitative real-time-PCR was used to detect FGF19 genetic amplification and FGF19 messenger RNA expression in LSCC tumor and paired adjacent samples. Small interfering RNA and short hairpin RNA were used to knockdown FGF19 in vitro and in vivo. RESULTS: FGF19 amplification was identified in a subset of LSCC patients (37.5%, 15/40), and upregulation of FGF19 expression was found in 60% (24/40) of tumor tissues compared to adjacent non-tumorous tissues. Correlation analysis with clinicopathologic parameters showed that FGF19 upregulation was significantly associated with heavy smoking. Small interfering RNA knockdown of FGF19 led to the significant inhibition of cell growth and induced apoptosis in LSCC cells carrying the amplified FGF19 gene, but these effects was not observed in non-amplified LSCC cells. Interfering FGF19 expression with short hairpin RNA also resulted in tumor growth inhibition and induced apoptosis in LSCC xenografts with amplified FGF19 in tumor cells. CONCLUSION: Our results suggested that FGF19 signaling activation is required for cell growth and survival of FGF19 amplified LSCC cells, both in vitro and in vivo. Intervention of FGF19 activation could be a potential therapeutic strategy for LSCC patients with FGF19 amplification. CI - (c) 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. FAU - Zhang, Xiaochen AU - Zhang X AD - Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Kong, Mei AU - Kong M AD - Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Zhang, Zhen AU - Zhang Z AD - Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China. FAU - Xu, Suzhen AU - Xu S AD - Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Yan, Feifei AU - Yan F AD - Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Wei, Liyuan AU - Wei L AD - Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Zhou, Jianying AU - Zhou J AUID- ORCID: 0000-0002-8924-935X AD - Department of Respiratory Disease, Thoracic Disease Centre, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. LA - eng PT - Journal Article DEP - 20170914 PL - Singapore TA - Thorac Cancer JT - Thoracic cancer JID - 101531441 RN - 0 (FGF19 protein, human) RN - 62031-54-3 (Fibroblast Growth Factors) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Apoptosis MH - Asian People/genetics MH - Carcinoma, Squamous Cell/*genetics MH - Cell Line, Tumor MH - Cell Proliferation MH - China/epidemiology MH - Female MH - Fibroblast Growth Factors/*genetics MH - *Gene Amplification MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*genetics MH - Male MH - Middle Aged MH - Smoking/epidemiology MH - Up-Regulation PMC - PMC5668513 OTO - NOTNLM OT - Apoptosis OT - FGF19 OT - cell proliferation OT - genetic amplification OT - lung squamous cell carcinoma EDAT- 2017/09/15 06:00 MHDA- 2018/03/21 06:00 PMCR- 2017/11/01 CRDT- 2017/09/15 06:00 PHST- 2017/07/06 00:00 [received] PHST- 2017/08/08 00:00 [revised] PHST- 2017/08/09 00:00 [accepted] PHST- 2017/09/15 06:00 [pubmed] PHST- 2018/03/21 06:00 [medline] PHST- 2017/09/15 06:00 [entrez] PHST- 2017/11/01 00:00 [pmc-release] AID - TCA12504 [pii] AID - 10.1111/1759-7714.12504 [doi] PST - ppublish SO - Thorac Cancer. 2017 Nov;8(6):655-665. doi: 10.1111/1759-7714.12504. Epub 2017 Sep 14.