Elementary studies on elevated steroidogenic factor-1 expression in aldosterone-producing adenoma

Urol Oncol. 2012 Jul-Aug;30(4):457-62. doi: 10.1016/j.urolonc.2010.03.001. Epub 2010 Sep 26.

Abstract

Objectives: The expression of steroidogenic factor-1 (SF-1) was elevated in adrenal aldosterone-producing adenoma (APA). The influence of SF-1 on adrenal tumorigenesis by adrenocortical cell line H295R cells was investigated.

Materials and methods: Real-time PCR and Western blotting were used to detect SF-1 expression in 16 APA samples and 12 normal adrenal samples. Specific SF-1-shRNA plasmid was transfected into H295R cells to inhibit SF-1 expression. Western blotting and real-time PCR were used to verify the effects of RNAi on SF-1 inhibition. Subsequently, WST-1 and cell count were applied to evaluate cell proliferation at different SF-1 levels. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to measure cell apoptosis, and proliferation marker Ki-67 was studied by immunohistochemistry.

Results: Compared with normal adrenal samples, SF-1 mRNA and protein levels in APA samples were significantly higher. It was 10.48:1 at SF-1 mRNA and 0.87 ± 0.05 vs. 0.39 ± 0.07 at protein levels, respectively (P < 0.01). A decreased SF-1 significantly inhibited cell proliferation in the experimental and control cells. These results were supported by weaker Ki-67 staining in SF-1-inhibited cells [(36.9% ± 4.17%) vs. (58.48% ± 7.16%) (P < 0.01)]. Moreover, SF-1 inhibition induced a 2.7-fold increase in the percentage of apoptotic H295R cells (P < 0.01).

Conclusions: Elevated SF-1 may play an important role in APA formation and primary aldosteronism. SF-1 acts as an oncogenic factor, and its inhibition provides new insight into the understanding and treatment of related adrenal diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics
  • Adrenal Cortex Neoplasms / metabolism*
  • Adrenal Cortex Neoplasms / pathology
  • Adrenocortical Adenoma / genetics
  • Adrenocortical Adenoma / metabolism*
  • Adrenocortical Adenoma / pathology
  • Aldosterone / biosynthesis*
  • Apoptosis
  • Blotting, Western
  • Cell Line
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Microscopy, Fluorescence
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroidogenic Factor 1 / genetics
  • Steroidogenic Factor 1 / metabolism*

Substances

  • Ki-67 Antigen
  • Steroidogenic Factor 1
  • Aldosterone