Data from: PCSK1N as a tumor size marker and an ER stress response protein in corticotroph pituitary adenomas

Purpose: Silent corticotroph adenoma (SCA) exhibits more tumor
aggressiveness features than functioning adenomas (FCA). We aimed to
investigate PCSK1N expression in CA and examine if ER stress-induced
responses affect cell survival in a corticotroph tumor cell model.
Methods: Clinical and imaging characteristics were recorded in 33 patients
with FCA (20 women,11 macroadenomas) and 18 SCA (8 women, all
macroadenomas). Gene expression of proopiomelanocortin (POMC), T-box
transcription factor 19(TBX19)/TPIT, proprotein convertase
subtilisin/kexin type 1(PCSK1)/PC1/3, and its inhibitor PCSK1N, was
measured by RT-qPCR in adenoma tissue. Mouse pituitary corticotroph tumor
(AtT-20) cells were treated with tanespimycin (17-AAG), a HSP90 chaperone
inhibitor, to induce ER stress followed by gene and protein analyses.
Results: POMC, TPIT, and PCSK1 expression were higher, whereas PCSK1N was
lower in FCA compared to SCA. PCSK1N correlated with POMC (rs= -0.514, p
<0.001), TPIT (rs= -0.386, p = 0.005), PCSK1 (rs= -0.3691, p =
0.008), and tumor largest diameter (rs= 0.645, p <0.001), in all
CA. Induction of ER stress by 17-AAG in AtT-20 cells led to a decrease of
POMC but an increase of PCSK1N gene expression at 24h. Moreover, a
downregulation of cell cycle, apoptosis, and senescence pathways, and
alterations in cell adhesion and cytoskeleton were observed at the protein
level. Conclusions: PCSK1N is higher in SCA compared with FCA,
and associated with corticotroph cell markers and tumor size. PCSK1N is
likely to be part of the adaptive response to ER stress, potentially
conferring a survival advantage to the corticotroph tumor cell in
conjunction with other proteins.