title: Tumor models for prostate cancer exemplified by fibroblast growth factor 8-induced tumorigenesis and tumor progression.
abstract: Prostate cancer is a very common malignancy among Western males. Although most tumors are indolent and grow slowly, some grow and metastasize aggressively. Because prostate cancer growth is usually androgen-dependent, androgen ablation offers a therapeutic option to treat post-resection tumor recurrence or primarily metastasized prostate cancer. However, patients often relapse after the primary response to androgen ablation therapy, and there is no effective cure for cases of castration-resistant prostate cancer (CRPC). The mechanisms of tumor growth in CRPC are poorly understood. Although the androgen receptors (ARs) remain functional in CRPC, other mechanisms are clearly activated (e.g., disturbed growth factor signaling). Results from our laboratory and others have shown that dysregulation of fibroblast growth factor (FGF) signaling, including FGF receptor 1 (FGFR1) activation and FGF8b overexpression, has an important role in prostate cancer growth and progression. Several experimental models have been developed for prostate tumorigenesis and various stages of tumor progression. These models include genetically engineered mice and rats, as well as induced tumors and xenografts in immunodeficient mice. The latter was created using parental and genetically modified cell lines. All of these models greatly helped to elucidate the roles of different genes in prostate carcinogenesis and tumor progression. Recently, patient-derived xenografts have been studied for possible use in testing individual, specific responses of tumor tissue to different treatment options. Feasible and functional CRPC models for drug responsiveness analysis and the development of effective therapies targeting the FGF signaling pathway and other pathways in prostate cancer are being actively investigated.
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tuomela
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland. Electronic address: harkonen@utu.fi.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Härkönen
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D051524:Fibroblast Growth Factor 8
keywords: Fibroblast growth factor; Patient-derived xenograft; Prostate cancer; Tumor model; Xenograft