CITED2 is expressed in human adrenocortical cells and regulated by basic fibroblast growth factor.
CITED2 gene deletion in mice leads to adrenal agenesis. Therefore, we analyzed CITED2, a CBP/p300 interacting transactivator with transforming activity, in the human adrenal gland. In this study, we examined CITED2 expression in human embryonic and adult adrenal glands as well as adrenocortical carcinomas. As ACTH and basic fibroblast growth factor (bFGF) are connected to the physiology and growth of adrenocortical cells we studied the regulation of CITED2 by these factors in the NCI-H295R adrenocortical carcinoma cell line. We found CITED2 expression in the adult adrenal cortex as well in adrenocortical carcinomas. At an early stage of human adrenal organogenesis CITED2 could be located to the definitive zone of the developing adrenal gland using immunohistochemistry. In NCI-H295R cells, stimulation by bFGF led to a dose-dependent increase in CITED2 promotor activity, mRNA and protein expression while ACTH had no significant effect. The stimulatory effect of bFGF could be reduced by blocking mitogen-activated protein kinase activity using the MAPkinase kinase (MEK1)-inhibitor PD98059. CITED2 is expressed in embryonic and adult human adrenal glands as well as in adrenocortical cancer. It is connected to the signaling cascades of bFGF and its expression is modulated by mitogen-activated protein kinases. This suggests a novel role for CITED2 in human adrenal growth and possibly in adrenal tumorigenesis.
Haase
Matthias
M
Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Moorenstr. 5, D-40225 Duesseldorf, Germany.
Schott
Matthias
M
Bornstein
Stefan R
SR
Malendowicz
Ludwik K
LK
Scherbaum
Werner A
WA
Willenberg
Holger S
HS
D000302:Adrenal Cortex / Q000737:chemistry / Q000196:embryology / Q000378:metabolism*; D018268:Adrenocortical Carcinoma; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods
C486381:CITED2 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D000324:Adrenocorticotropic Hormone