Schwertfeger Kathryn L
University of Minnesota, Department of Lab Medicine and Pathology, Masonic Cancer Center. 420 Delaware St. SE, MMC 609, Minneapolis, MN 55455, USA.
Curr Drug Targets. 2009 Jul;10(7):632-44. doi: 10.2174/138945009788680419.
The fibroblast growth factor (FGF) family is comprised of 22 ligands that bind and activate several FGF receptor (FGFR) isoforms. Critical roles for FGFs and FGFRs have been well-established during embryonic development. For example, the FGF10/FGFR2IIIb axis has been linked to embryonic development of both the mammary and prostate glands, which are the subject of this review. Furthermore, recent studies using novel mouse models have suggested that this pathway also participates in postnatal development in the mammary and prostate glands. These studies have provided novel insights into the mechanisms by which FGFs and FGFRs promote ductal outgrowth and branching morphogenesis. In addition to the established roles of FGFs in development, aberrant activation of the FGF pathway has been linked to tumor progression in both breast and prostate cancer. Recent studies have linked FGFR1 expression and single nucleotide polymorphisms in FGFR2 to breast cancer. Furthermore, novel pre-clinical models have demonstrated the ability of FGFRs to promote numerous aspects of breast and prostate cancer. Understanding the roles of FGFs in development will provide insights into the mechanisms by which deregulation of the FGF pathway leads to tumorigenesis, ultimately leading to the development of novel therapeutic strategies designed to target this pathway in cancer patients.
成纤维细胞生长因子(FGF)家族由22种配体组成,这些配体可结合并激活多种FGF受体(FGFR)亚型。FGF和FGFR在胚胎发育过程中的关键作用已得到充分证实。例如,FGF10/FGFR2IIIb轴与乳腺和前列腺的胚胎发育有关,而这正是本综述的主题。此外,最近使用新型小鼠模型的研究表明,该通路也参与乳腺和前列腺的出生后发育。这些研究为FGF和FGFR促进导管生长和分支形态发生的机制提供了新的见解。除了FGF在发育中的既定作用外,FGF通路的异常激活与乳腺癌和前列腺癌的肿瘤进展有关。最近的研究将FGFR1的表达和FGFR2中的单核苷酸多态性与乳腺癌联系起来。此外,新的临床前模型已经证明FGFR能够促进乳腺癌和前列腺癌的多个方面。了解FGF在发育中的作用将有助于深入了解FGF通路失调导致肿瘤发生的机制,最终推动开发旨在针对癌症患者该通路的新型治疗策略。