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POD-1 binding to the E-box sequence inhibits SF-1 and StAR expression in human adrenocortical tumor cells

Monica Malheiros França1, Bruno Ferraz-de-Souza, Mariza Gerdulo Santos

  • 1Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, SP, Brazil.

Molecular and Cellular Endocrinology
|January 15, 2013
PubMed

Insights

Pod-1/Tcf21 inhibits Steroidogenic Factor-1 (SF-1) expression in adrenocortical tumor cells, impacting SF-1 target genes like StAR. Overexpression of POD-1 did not affect cell viability but correlated with cell cycle pathways in human ACCs.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Pod-1/Tcf21 is involved in organ development and known to inhibit Steroidogenic Factor-1 (SF-1) during gonadal development.
  • SF-1 disruption causes adrenal disorders, while its overexpression is linked to adrenal cell proliferation and tumorigenesis.

Purpose of the Study:

  • To investigate if POD-1 overexpression inhibits endogenous SF-1 expression in human and mouse adrenocortical tumor cells.
  • To determine the effect of POD-1 on SF-1 target genes and cell cycle pathways in adrenocortical carcinoma (ACC).

Main Methods:

  • Transient transfection of adrenocortical cells (mouse Y-1, human H295R, ACC-T36) with POD-1 expression vectors and SF-1 promoter-luciferase reporter.
  • Chromatin immunoprecipitation (ChIP) assay to confirm POD-1 binding to the SF-1 promoter.
  • Analysis of SF-1 target gene StAR expression and correlation of POD-1/TCF21 with KEGG pathways in human ACCs.

Main Results:

  • POD-1 inhibited SF-1 promoter-driven luciferase reporter gene transcription in a dose-dependent manner.
  • POD-1 overexpression suppressed endogenous SF-1 expression in human and mouse ACC cells.
  • ChIP assay confirmed POD-1 binding to the E-box sequence in the SF-1 promoter.
  • POD-1 overexpression decreased the expression of the SF-1 target gene, StAR.
  • Induced POD-1 expression did not affect cell viability but was negatively correlated with cell cycle genes in human ACCs.

Conclusions:

  • POD-1/Tcf21 acts as a transcriptional repressor of SF-1 in adrenocortical tumor cells.
  • POD-1 influences SF-1-mediated pathways, including StAR expression, and is associated with cell cycle regulation in adrenocortical tumors.

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