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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2015 > Volume 11 Number 8 > Yanqing Huang1, Chengliu Jin1, Tomoaki Hamana1, Junchen Liu1, Cong Wang2, Lei An1, Wallace L. McKeehan1, and Fen Wang1,2,3

Overexpression of FGF9 in Prostate Epithelial Cells Augments Reactive Stroma Formation and Promotes Prostate Cancer Progression

Yanqing Huang1, Chengliu Jin1, Tomoaki Hamana1, Junchen Liu1, Cong Wang2, Lei An1, Wallace L. McKeehan1, and Fen Wang1,2,3
Yanqing Huang1, Chengliu Jin1#, Tomoaki Hamana1, Junchen Liu1, Cong Wang2, Lei An1, Wallace L. McKeehan1, and Fen Wang1,2,3 1. Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USA 2. Wenzhou Medical College, Wenzhou, Zhejiang, China 3. Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M, Health Science Center, College Station, TX, USA. Current address: Transgenic and Gene Targeting Core, Georgia State University, Atlanta, GA, USA Corresponding author: Fen Wang, Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030-3303. E-mail: fwang@ibt.tamhsc.edu
Abstract :

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 leveland 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.

Keywords :
fibroblast growth factor, receptor tyrosine kinase, conditional gene knockout, prostate cancer progression, EMT, reactive stroma.

Date Deposited : 01 Mar 2016 10:52

Last Modified : 01 Mar 2016 10:52

Official URL: http://www.ijbs.com/v11i8

Volume 11, Number 8, - 2015 , ISSN 1449-2288

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