EGFR Induces E2F1-Mediated Corticotroph Tumorigenesis.

ABSTRACT: The epidermal growth factor receptor (EGFR), expressed in adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas causing Cushing disease, regulates ACTH production and corticotroph proliferation. To elucidate the utility of EGFR as a therapeutic target for Cushing disease, we generated transgenic (Tg) mice with corticotroph-specific human EGFR expression (corti-EGFR-Tg) using a newly constructed corticotroph-specific promoter. Pituitary-specific EGFR expression was observed by 2.5 months, and aggressive ACTH-secreting pituitary adenomas with features of Crooke's cells developed by 8 months with 65% penetrance observed. Features consistent with the Cushing phenotype included elevated plasma ACTH and corticosterone levels, increased body weight, glucose intolerance, and enlarged ad

SUBMITTER: Araki T 

PROVIDER: S-EPMC5686559 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature