ErbB receptor-Driven prolactinomas respond to targeted lapatinib treatment in female transgenic mice

Xiaohai Liu, Maya Kano, Takako Araki, Odelia Cooper, Hidenori Fukuoka, Yukiko Tone, Masahide Tone, Shlomo Melmed

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

As ErbB receptors are expressed in prolactinomas and exhibit downstream effects on prolactin (PRL) production and cell proliferation, we generated transgenic mice using a PRL enhancer/promoter expression system to restrict lactotroph-specific expression of human epidermal growth factor receptor (EGFR) or human EGFR2 (HER2). EGFR or HER2 transgenic mice developed prolactinomas between 13 and 15 months, and confocal immunofluorescence and Western blot analysis confirmed lactotroph-restricted PRL and EGFR or HER2 coexpression. Circulating PRL levels in EGFR and HER2 transgenic mice were increased 5- and 3.8-fold, respectively. Inhibiting EGFR or HER2 signaling with oral lapatinib (100 mg/kg), a dual tyrosine kinase inhibitor for both EGFR and HER2, suppressed circulating PRL by 72% and attenuated tumor PRL expression by 80% and also attenuated downstream tumor EGFR/HER2 signaling. This model demonstrates the role of ErbB receptors underlying prolactinoma tumorigenesis and the feasibility of targeting these receptors for translation to treatment of refractory prolactinomas.

Original languageEnglish (US)
Pages (from-to)71-79
Number of pages9
JournalEndocrinology
Volume156
Issue number1
DOIs
StatePublished - Jan 1 2015

Bibliographical note

Publisher Copyright:
© 2015 by the Endocrine Society.

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