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WNT-4 mRNA expression in human adrenocortical tumors and cultured adrenal cells
T Kuulasmaa1, J Jääskeläinen, S Suppola
1Department of Pediatrics, Kuopio University and University Hospital, Kuopio, Finland.
Abstract:
The members of the Wnt glycoprotein family are important in embryogenesis and adult tissue homeostasis, and deletion of WNT-4 gene in mice leads to improper development of many organs including the adrenals. The objective of this study was to investigate the expression of WNT-4 gene in human adrenals and adrenocortical tumors. The WNT-4 mRNA expression (analyzed by quantitative real-time RT-PCR) was significantly higher in Conn's adenomas (p<0.01) and lower in Cushing's adenomas, virilizing carcinomas and fetal adrenals (p<0.05) compared with normal adult adrenals. WNT-4 mRNA expression was clearly upregulated by ACTH and 8-bromo-cAMP (8-BrcAMP) in primary cultures of normal adult adrenocortical cells, but downregulated by 8-BrcAMP and 12- O-tetradecanoylphorbol-13-acetate (TPA) in human NCI-H295R adrenocortical carcinoma cells. Angiotensin II tended to increase WNT-4 mRNA expression at 24 hours and decreased it at 48 hours time point in both cell culture types. The abundant WNT-4 mRNA expression in Conn's adenomas and its hormonal regulation in adrenocortical cells suggest a role for WNT-4 in human adrenocortical function.
Insights
WNT-4 gene expression varies in human adrenal tissues and tumors. Its regulation by hormones suggests a role in adrenal function, particularly in Conn
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- Wnt glycoproteins are crucial for embryogenesis and tissue maintenance.
- WNT-4 gene mutations in mice cause developmental defects, including in adrenal glands.
Purpose of the Study:
- To examine WNT-4 gene expression in human adrenal tissues and tumors.
- To understand the hormonal regulation of WNT-4 in adrenocortical cells.
Main Methods:
- Quantitative real-time RT-PCR was used to analyze WNT-4 mRNA levels.
- Primary cultures of normal adult adrenocortical cells and NCI-H295R cells were used.
- Cells were treated with hormones like ACTH, 8-bromo-cAMP, TPA, and Angiotensin II.
Main Results:
- WNT-4 mRNA was significantly higher in Conn's adenomas and lower in Cushing's adenomas, virilizing carcinomas, and fetal adrenals compared to normal adult adrenals.
- ACTH and 8-bromo-cAMP upregulated WNT-4 in normal cells.
- 8-bromo-cAMP and TPA downregulated WNT-4 in NCI-H295R cells.
- Angiotensin II showed time-dependent effects on WNT-4 expression in both cell types.
Conclusions:
- WNT-4 gene expression is altered in specific human adrenocortical tumors.
- Hormonal factors modulate WNT-4 expression in adrenocortical cells.
- WNT-4 likely plays a role in human adrenal function and tumorigenesis.
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