FGF23 promotes prostate cancer progression

被引:77
作者
Feng, Shu [1 ,2 ]
Wang, Jianghua [1 ,2 ]
Zhang, Yiqun [3 ]
Creighton, Chad J. [3 ,4 ]
Ittmann, Michael [1 ,2 ]
机构
[1] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA
[2] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA
[3] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
关键词
prostate cancer; FGF23; signal transduction; fibroblast growth factors; endocrine fibroblast growth factors; GROWTH-FACTOR; SERUM-CALCIUM; FUSION; GENE; RECEPTOR; CELLS; DIFFERENTIATION; EXPRESSION; PROGNOSIS; PATHWAYS;
D O I
10.18632/oncotarget.4174
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Prostate cancer is the most common cancer in US men and the second leading cause of cancer deaths. Fibroblast growth factor 23 (FGF23) is an endocrine FGF, normally expressed by osteocytes, which plays a critical role in phosphate homeostasis via a feedback loop involving the kidney and vitamin D. We now show that FGF23 is expressed as an autocrine growth factor in all prostate cancer cell lines tested and is present at increased levels in prostate cancer tissues. Exogenous FGF23 enhances proliferation, invasion and anchorage independent growth in vitro while FGF23 knockdown in prostate cancer cell lines decreases these phenotypes. FGF23 knockdown also decreases tumor growth in vivo. Given that classical FGFs and FGF19 are also increased in prostate cancer, we analyzed expression microarrays hybridized with RNAs from of LNCaP cells stimulated with FGF2, FGF19 or FGF23. The different FGF ligands induce overlapping as well as unique patterns of gene expression changes and thus are not redundant. We identified multiple genes whose expression is altered by FGF23 that are associated with prostate cancer initiation and progression. Thus FGF23 can potentially also act as an autocrine, paracrine and/or endocrine growth factor in prostate cancer that can promote prostate cancer progression.
引用
收藏
页码:17291 / 17301
页数:11
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