FGF19 genetic amplification as a potential therapeutic target in lung squamous cell carcinomas.

Abstract:

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.

journal_name

Thorac Cancer

journal_title

Thoracic cancer

authors

Zhang X,Kong M,Zhang Z,Xu S,Yan F,Wei L,Zhou J

doi

10.1111/1759-7714.12504

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

655-665

issue

6

eissn

1759-7706

issn

1759-7714

journal_volume

8

pub_type

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