WNT-4 mRNA expression in human adrenocortical tumors and cultured adrenal cells.
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.
Department of Pediatrics, Kuopio University and University Hospital, Kuopio, Finland.
T
T
Kuulasmaa
J
J
Jääskeläinen
S
S
Suppola
T
T
Pietiläinen
P
P
Heikkilä
S
S
Aaltomaa
V-M
VM
Kosma
R
R
Voutilainen
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D000311:Adrenal Glands / Q000166:cytology* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060528:Wnt4 Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D051176:beta Catenin; D000804:Angiotensin II; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000324:Adrenocorticotropic Hormone; D013755:Tetradecanoylphorbol Acetate