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2017 ; 8
(34
): 57072-57088
Nephropedia Template TP
gab.com Text
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English Wikipedia
Notch system is differentially expressed and activated in pituitary adenomas of
distinct histotype, tumor cell lines and normal pituitaries
#MMPMID28915655
Perrone S
; Zubeldia-Brenner L
; Gazza E
; Demarchi G
; Baccarini L
; Baricalla A
; Mertens F
; Luque G
; Vankelecom H
; Berner S
; Becu-Villalobos D
; Cristina C
Oncotarget
2017[Aug]; 8
(34
): 57072-57088
PMID28915655
show ga
Pituitary adenomas are among the most frequent intracranial neoplasms and
treatment depends on tumor subtype and clinical features. Unfortunately, non
responder cases occur, then new molecular targets are needed. Notch system
component expression and activation data are scarce in pituitary tumorigenesis,
we therefore aimed to characterize Notch system in pituitary tumors of different
histotype. In human pituitary adenomas we showed NOTCH1-4 receptors, JAGGED1
ligand and HES1 target gene expression with positive correlations between
NOTCH1,2,4 and HES1, and NOTCH3 and JAGGED1 denoting Notch system activation in a
subset of tumors. Importantly, NOTCH3 positive cells were higher in
corticotropinomas and somatotropinomas compared to non functioning adenomas. In
accordance, Notch activation was evidenced in AtT20 tumor corticotropes, with
higher levels of NOTCH1-3 active domains, Jagged1 and Hes1 compared to normal
pituitary. In the prolactinoma cell lines GH3 and MMQ, in vivo GH3 tumors and
normal glands, Notch system activation was lower than in corticotropes. In MMQ
cells only the NOTCH2 active domain was increased, whereas NOTCH1 active domain
was higher in GH3 tumors. High levels of Jagged1 and Dll1 were found solely in
GH3 cells, and Hes1, Hey1 and Hey2 were expressed in a model dependent pattern.
Prolactinomas harbored by lacDrd2KO mice expressed high levels of NOTCH1 active
domain and reduced Hes1. We show a differential expression of Notch system
components in tumoral and normal pituitaries and specific Notch system
involvement depending on adenoma histotype, with higher activation in
corticotropinomas. These data suggest that targeting Notch pathway may benefit
non responder pituitary adenomas.