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Vitamin D receptor activation is a feasible therapeutic target to impair adrenocortical tumorigenesis

Ana Carolina Bueno1, Candy Bellido More1, Junier Marrero-Gutiérrez2

  • 1Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.

Molecular and Cellular Endocrinology
|September 1, 2022
PubMed
Abstract

Insights

Vitamin D Receptor (VDR) signaling shows therapeutic potential in adrenocortical carcinoma (ACC). Restoring VDR function inhibits tumor growth and steroid secretion, offering a new treatment avenue for ACC.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Adrenocortical carcinoma (ACC) is a rare endocrine malignancy.
  • Dysregulation of Vitamin D Receptor (VDR) signaling is implicated in cancer development.
  • Understanding VDR's role in ACC is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the therapeutic potential of VDR signaling in ACC.
  • To evaluate the effects of VDR activation on ACC cell behavior and tumorigenesis.
  • To explore VDR's methylation status and its impact on VDR expression in ACC.

Main Methods:

  • Assessed VDR methylation and expression in H295R ACC cells.
  • Treated ACC cells with calcitriol and seocalcitol to modulate VDR signaling.
  • Utilized RNA sequencing to analyze gene expression changes post-treatment.
  • Evaluated the in vivo effects of seocalcitol on ACC xenografts.

Main Results:

  • VDR was found to be hypermethylated and underexpressed in basal ACC cells.
  • Calcitriol and seocalcitol treatments restored VDR signaling, exhibiting antiproliferative effects.
  • VDR activation modulated steroid hormone biosynthesis and Rap1 signaling pathways.
  • Seocalcitol inhibited tumor growth in vivo without causing hypercalcemia.

Conclusions:

  • VDR hypermethylation contributes to VDR underexpression and signaling inactivation in ACC.
  • VDR signaling demonstrates significant antiproliferative effects in vitro and in vivo.
  • VDR represents a promising therapeutic target for adrenocortical carcinoma treatment.
Keywords:
Adrenocortical tumorH295R cellsTarget therapyVitamin D receptor

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