Vitamin D receptor activation is a feasible therapeutic target to impair adrenocortical tumorigenesis.
Mol Cell Endocrinol
; 558: 111757, 2022 12 01.
Article
en En
| MEDLINE
| ID: mdl-36049598
ABSTRACT
OBJECTIVE:
To evaluate the therapeutic potential of vitamin D receptor (VDR) signaling in adrenocortical carcinoma (ACC) cells.METHODS:
We evaluated VDR's methylation pattern in H295R ACC cells, and investigated the effects of calcitriol and seocalcitol treatments on adrenocortical tumorigenesis.RESULTS:
VDR was hypermethylated and underexpressed in basal H295R cells. Treatments with calcitriol and seocalcitol restored VDR signaling, resulted in antiproliferative effects, and impaired Wnt/B-catenin signaling. RNAseq of treated cells demonstrated VDR activation on steroid hormones biosynthesis and Rap1 signaling, among others. In vivo, seocalcitol constrained the growth of H295R xenografts and reduced autonomous tumor steroid secretion without hypercalcemia-associated side effects.CONCLUSIONS:
H295R cells present VDR hypermethylation, which can be responsible for its underexpression and signaling inactivation under basal conditions. VDR signaling promoted antiproliferative effects in vitro and in vivo, suggesting that it may be a potential therapeutic target for ACC and a valuable tool for patient's clinical management.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Corteza Suprarrenal
/
Carcinoma Corticosuprarrenal
Idioma:
En
Revista:
Mol Cell Endocrinol
Año:
2022
Tipo del documento:
Article