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Updated: Jul 7, 2026
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Published on: September 30, 2016
Targeted expression of a human pituitary tumor-derived isoform of FGF receptor-4 recapitulates pituitary
Shereen Ezzat1, Lei Zheng, Xian-Feng Zhu
1Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Abstract:
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.
Insights
Researchers discovered a new pituitary tumor-specific form of FGF receptor-4 (ptd-FGFR4). This altered receptor drives pituitary tumor formation and mimics human pituitary disease, offering new insights into tumor development.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Pituitary gland tumors affect up to 20% of individuals.
- The molecular mechanisms driving pituitary tumor development are not well understood.
Purpose of the Study:
- To identify novel molecular players involved in pituitary tumorigenesis.
- To characterize a newly identified pituitary tumor-derived FGF receptor-4 (ptd-FGFR4) isoform.
Main Methods:
- Identification and characterization of the ptd-FGFR4 mRNA and protein.
- In vitro and in vivo transformation assays.
- Targeted expression studies in mouse models.
Main Results:
- A novel, N-terminally truncated FGFR4 isoform (ptd-FGFR4) was identified, arising from alternative transcription.
- ptd-FGFR4 exhibits constitutive phosphorylation and transforming activity in vitro and in vivo.
- Targeted expression of ptd-FGFR4, but not wild-type FGFR4, induced pituitary tumors resembling human disease.
Conclusions:
- ptd-FGFR4 is a key driver of pituitary tumorigenesis.
- This discovery provides a new molecular target for understanding and potentially treating pituitary tumors.
