Overexpression of FGF9 in prostate epithelial cells augments reactive stroma formation and promotes prostate cancer progression.
Overexpression of FGF9 in prostate epithelial cells augments reactive stroma formation and promotes prostate cancer progression.
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前列腺上皮细胞中 FGF9 的过度表达增强反应性基质形成并促进前列腺癌进展
DOI：
10.7150/ijbs.12468
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发表时间：
2015
影响因子：
9.2
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Huang Y;Jin C;Hamana T;Liu J;Wang C;An L;McKeehan WL;Wang F
骨转移是前列腺癌发病和死亡的主要原因。已报道成纤维细胞生长因子9（FGF 9）促进PCa骨转移。然而，FGF 9过表达促进PCa进展和转移的机制仍不清楚。在此，我们报告，转基因小鼠被迫表达FGF 9在前列腺上皮细胞（F9 TG）发展高级别前列腺上皮内瘤（PIN）的表达水平和时间依赖性的方式。此外，FGF 9/TRAMP双基因小鼠（F9 TRAMP）比TRAMP同窝小鼠更早生长晚期PCa并且具有更高的转移频率。我们观察到肿瘤微环境的变化，包括F9 TG和F9 TRAMP小鼠间质区室中的细胞过多和过度增殖。在F9 TG和F9 TRAMP前列腺中，TGFβ1（一种在反应性基质中过表达的关键信号分子）的表达增加。体内和体外数据均表明，FGF 9通过增加cJun介导的信号传导促进TGFβ1的表达。此外，计算机模拟分析显示，在人前列腺癌中，FGF 9的表达水平与TGFβ1及其下游信号分子的表达呈正相关。总的来说，我们的数据表明，在PCa细胞中过度表达FGF 9增加了反应性基质的形成，促进了PCa的发生和进展。
Bone metastasis is the major cause of morbidity and mortality of prostate cancer (PCa). Fibroblast growth factor 9 (FGF9) has been reported to promote PCa bone metastasis. However, the mechanism by which overexpression of FGF9 promotes PCa progression and metastasis is still unknown. Herein, we report that transgenic mice forced to express FGF9 in prostate epithelial cells (F9TG) developed high grade prostatic intraepithelial neoplasia (PIN) in an expression level- and time-dependent manner. Moreover, FGF9/TRAMP bigenic mice (F9TRAMP) grew advanced PCa earlier and had higher frequencies of metastasis than TRAMP littermates. We observed tumor microenvironmental changes including hypercellularity and hyperproliferation in the stromal compartment of F9TG and F9TRAMP mice. Expression of TGFβ1, a key signaling molecule overexpressed in reactive stroma, was increased in F9TG and F9TRAMP prostates. Both in vivo and in vitro data indicated that FGF9 promoted TGFβ1 expression via increasing cJun-mediated signaling. Moreover, in silico analyses showed that the expression level of FGF9 was positively associated with expression of TGFβ1 and its downstream signaling molecules in human prostate cancers. Collectively, our data demonstrated that overexpressing FGF9 in PCa cells augmented the formation of reactive stroma and promoted PCa initiation and progression.
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影响因子：
4.6
作者：
Lin, Yongshun;Liu, Guoqin;Wang, Fen
通讯作者：
Wang, Fen
影响因子：
11.2
作者：
Jin, CL;Wang, F;McKeehan, WL
通讯作者：
McKeehan, WL
影响因子：
50.3
作者：
Acevedo, Victor D.;Gangula, Rama D.;Spencer, David M.
通讯作者：
Spencer, David M.
DOI：
10.1093/jnci/93.23.1783
发表时间：
2001-12-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Ozen, M;Giri, D;Ittmann, M
通讯作者：
Ittmann, M
影响因子：
4.8
作者：
SantosOcampo, S;Colvin, JS;Ornitz, DM
通讯作者：
Ornitz, DM