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

Abstract

BackgroundAlthough FGF 19 gene aberrations are associated with carcinogenesis and progression in human cancers, the roles of FGF 19 genetic amplification and expression in Chinese patients with lung squamous cell carcinoma (LSCC) and FGF 19 amplification as a potential therapeutic target for LSCC are not well understood.MethodsFluorescence in situ hybridization analysis and quantitative real‐time‐PCR was used to detect FGF 19 genetic amplification and FGF 19 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 FGF 19 amplification was identified in a subset of LSCC patients (37.5%, 15/40), and upregulation of FGF 19 expression was found in 60% (24/40) of tumor tissues compared to adjacent non‐tumorous tissues. Correlation analysis with clinicopathologic parameters showed that FGF 19 upregulation was significantly associated with heavy smoking. Small interfering RNA knockdown of FGF 19 led to the significant inhibition of cell growth and induced apoptosis in LSCC cells carrying the amplified FGF 19 gene, but these effects was not observed in non‐amplified LSCC cells. Interfering FGF 19 expression with short hairpin RNA also resulted in tumor growth inhibition and induced apoptosis in LSCC xenografts with amplified FGF 19 in tumor cells.ConclusionOur results suggested that FGF 19 signaling activation is required for cell growth and survival of FGF 19 amplified LSCC cells, both in vitro and in vivo. Intervention of FGF 19 activation could be a potential therapeutic strategy for LSCC patients with FGF 19 amplification.