Exp Clin Endocrinol Diabetes 2007; 115 - P02_049
DOI: 10.1055/s-2007-972456

CITED2 expression and its regulation in human adrenocortical cancer

M Haase 1, M Schott 1, SR Bornstein 2, LK Malendowicz 3, WA Scherbaum 1, HS Willenberg 1
  • 1Universitätsklinikum Düsseldorf, Klinik für Endokrinologie, Diabetologie und Rheumatologie, Düsseldorf, Germany
  • 2Medizinische Akademie Carl-Gustav-Carus, Universitätsklinik III, Dresden, Dresden, Germany
  • 3University of Poznan, School of Medicine, Poznan, Poland

CITED2, a CBP/p300 interacting transactivator, has been shown to be essential for murine adrenal development. Its overexpression leads to enhanced proliferation in different cell models and to oncogenic cell transformation.

Here were analyzed immunohistochemically the expression of CITED2 in adrenocortical cancer as well as its regulation in the adrenocortical cancer cell line NCI-H295R by different factors including basic fibroblast growth factor (bfGF) and corticotropin (ACTH).

Immunohistochemistry demonstrated CITED2 expression in adrenocortical cancer represented by a strong nuclear staining signal. In NCI-H295R cells CITED2 promotor-activity, mRNA-level and protein-level were significantly increased by the stimulation with bFGF in a dose-dependant manner. The inhibition of mitogen-activated protein kinases (MAPK), applying the MEK1-inhibitor PD98059, reduced the stimulatory effects of bFGF. However, ACTH did not exert an effect on the expression of CITED2, although its receptor was expressed on the cancer cells.

In conclusion, CITED2 is expressed in adrenocortical cancer cells and under control of bFGF involving a MAPK pathway. Since bFGF and MAPKs are clearly associated with adrenal growth and proliferation this could implicate an integration of CITED2 in growth related processes in adrenocortical cells and possibly in adrenocortical tumorigenesis.