Overexpression of FGF9 in prostate epithelial cells augments reactive stroma formation and promotes prostate cancer progression

Yanqing Huang, Chengliu Jin, Tomoaki Hamana, Junchen Liu, Cong Wang, Lei An, Wallace L. McKeehan, Fen Wang

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)948-960
Number of pages13
JournalInternational Journal of Biological Sciences
Volume11
Issue number8
DOIs
StatePublished - Jun 11 2015

Keywords

  • Conditional gene knockout
  • EMT
  • Fibroblast growth factor
  • Prostate cancer progression
  • Reactive stroma
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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