J Clin Invest, January 2002, Volume 109, Number 1, 69-78
Copyright ©2002 by the American Society for Clinical Investigation
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Article
Targeted expression of a human pituitary tumor–derived isoform of FGF receptor-4 recapitulates pituitary tumorigenesis
Shereen Ezzat1,2, Lei Zheng1,2, Xian-Feng Zhu1,2, Gillian E. Wu3,4 and Sylvia L. Asa2,4,5
1 Department of Medicine, University of Toronto, Toronto, Ontario, Canada 2 The Freeman Centre for Endocrine Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada 3 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada 4 Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada 5 Department of Pathology and Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada
Address correspondence to: Sylvia L. Asa, Ontario Cancer Institute, 610 University Avenue, Room 4-302, Toronto, Ontario, Canada M5G-2M9. Phone: (416) 946-2099; Fax: (416) 946-6579; E-mail: sylvia.asa@uhn.on.ca.
Received for publication August 22, 2001, and accepted in revised form October 29, 2001.
It is estimated that up to one in five individuals develop pituitary gland tumors. Despite the common occurrence of these tumors, the pathogenetic mechanisms underlying their development remain largely unknown. We report the identification of a novel pituitary tumor–derived, N-terminally truncated isoform of FGF receptor-4 (ptd-FGFR4). The corresponding mRNA results from alternative transcription initiation and encodes a polypeptide that lacks a signal peptide and the first two extracellular Ig-like domains. ptd-FGFR4 has a distinctive cytoplasmic residence, is constitutively phosphorylated, and is transforming in vitro and in vivo. Here we show that targeted expression of ptd-FGFR4, but not FGFR4, results in pituitary tumors that morphologically recapitulate the human disease. |
