Abstract
Cushing disease (CD) is a rare disorder with severe sequels and incompletely understood pathogenesis. The underlying corticotroph adenomas harbor frequently somatic mutations in the ubiquitin-specific peptidase 8 (USP8) gene. These mutations render USP8 hyperactive and prevent client proteins from degradation. Objective: To investigate the impact of USP8 mutations on proteins deregulated in CD. Design: One hundred eight pituitary adenomas (75 corticotroph [58 USP8 wild type (WT) and 17 USP8 mutated], 14 somatotroph, and 19 nonfunctioning) were investigated by immunohistochemistry. All evaluated proteins [USP8, arginine vasopressin receptor 1b and 2, corticotropinreleasing hormone receptor, cAMP response element-binding protein (CREB), p27/kip1, cyclin E, heat shock protein 90 (HSP90), orphan nuclear receptor 4, epidermal growth factor receptor, histone deacetylase 2, glucocorticoid receptor, cyclin-dependent kinase 5 and Abelson murine leukemia viral oncogene homolog 1 enzyme substrate 1] were known to be deregulated in CD. Furthermore, AtT20 cells were transfected with USP8 to investigate the expression of possible downstream proteins by immunoblot.
Original language | English |
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Pages (from-to) | 2535-2546 |
Number of pages | 12 |
Journal | Journal of Clinical Endocrinology and Metabolism |
Volume | 104 |
Issue number | 7 |
Early online date | 7 Mar 2019 |
DOIs | |
Publication status | Published - Jul 2019 |
Keywords
- USP8 mutations
- Cushing's disease
- AVPR1b
- CRHR
- p27
- HSP90
- CREB
- TR4
- cyclinE
- EGFR