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Horm Metab Res 2005; 37(6): 355-360
DOI: 10.1055/s-2005-870151
Review
© Georg Thieme Verlag KG Stuttgart · New York

FGF Receptor Signaling at the Crossroads of Endocrine Homeostasis and Tumorigenesis

S.  Ezzat1 , S.  L.  Asa2
  • 1Departments of Medicine, University of Toronto, Endocrine Oncology Site Group, Mount Sinai & Princess Margaret Hospitals, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
  • 2Pathology and Laboratory Medicine, University of Toronto, Endocrine Oncology Site Group, Mount Sinai & Princess Margaret Hospitals, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
Further Information

Publication History

Received 5 August 2004

Accepted after revision 20 September 2004

Publication Date:
07 July 2005 (online)

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Abstract

Multiple endocrine neoplasia (MEN) syndromes represent familial disorders characterized by endocrine cell growth and hormone production dysregulation. For several decades, the fibroblast growth factor (FGF) system has been suspected of playing a unique function in MEN-type I (MEN I). However, specific elucidation of these actions has been hampered by the overwhelming redundancy of this complex system. The human FGF family is composed of 22 members organized into 6 groups based on phylogenetic relationships. Signaling is mediated through membrane-spanning tyrosine kinase receptors encoded by four independent genes, some of which generate multiple products via alternative splicing or transcription initiation. High-affinity interaction between an FGF and its cognate receptor induces receptor dimerization and activation. Many FGFs display high-affinity interactions with multiple FGFRs, while some activate unique receptors or receptor isoforms. Most FGFs have demonstrated mitogenic activity in a variety of systems; however, a growing number display predominantly metabolic actions. This review will examine the evidence that FGF/FGFRs play a role in sporadic endocrine neoplasia and the pathways in which these molecules may be selectively targeted for therapeutic purposes.

Key words

FGF - FGF receptors - Pituitary tumors - Pancreatic neuroendocrine tumors

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Dr. S. Ezzat

Princess Margaret Hospital · Pathology - 4-302

610 University Avenue · Toronto · Ontario · Canada · M5G-2M9

Phone: +1 (416) 946-2088

Fax: +1 (416) 586-8834

Email: sezzat@mtsinai.on.ca