title: FGF23 promotes prostate cancer progression.
abstract: 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.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas, USA.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, Texas, USA.|Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine and Michael E. DeBakey Dept. of Veterans Affairs Medical Center, Houston, Texas, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ittmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: FGF23; endocrine fibroblast growth factors; fibroblast growth factors; prostate cancer; signal transduction