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Horm Metab Res 2004; 36(6): 397-405
DOI: 10.1055/s-2004-814563
Review
© Georg Thieme Verlag Stuttgart · New York

Role of the Insulin-like Growth Factor System in Adrenocortical Growth Control and Carcinogenesis

Ch.  Fottner 1 , A.  Hoeflich 2 , E.  Wolf 2 , M.  M.  Weber 1
  • 1Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, I. Medizinische Klinik und Poliklinik, Johannes Gutenberg University, Mainz, Germany
  • 2Institute of Molecular Animal Breeding/Gene Center, Ludwig Maximilians University of Munich, Germany
Further Information

Publication History

Received 8 December 2003

Accepted after Revision 9 March 2004

Publication Date:
07 July 2004 (online)

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Abstract

Clinically silent adrenocortical adenomas are the most frequent abnormalities in the adrenal gland. In contrast, adrenocortical carcinoma is a rare tumor with an extremely poor prognosis. The factors responsible for the frequent occurrence of benign adrenocortical tumors on one hand and the rare malignant transformation on the other are not known. Several genetic alterations such as loss of imprinting or loss of heterozygosity of the 11p15 gene locus causing a strong IGF-II overexpression have been demonstrated in the majority of adrenocortical carcinomas. In addition to IGF-II overexpression, increased levels of the IGF-I-receptor and IGFBP-2 have been found in advanced human adrenocortical carcinomas, suggesting an important role for the IGF-system in adrenocortical carcinogenesis. IGFs are potent mitogens regulating growth and apoptosis through interaction with the IGF-I-receptor, and overexpression of the human IGF-I-receptor promotes ligand-dependent neoplastic transformation in a variety of different cell systems. It is evident, therefore, that high levels of IGF-II in combination with overexpression of the IGF-I-receptor can provide a significant growth advantage for adrenocortical carcinoma cells and thus contribute to the highly malignant phenotype of this rare type of cancer. Additionally, it has been shown that overexpression of IGFBP-2 can promote malignant transformation of Y1 mouse adrenocortical tumor cells through unknown IGF-independent mechanisms. As one possible mechanism, we have recently found altered expression of catalase in IGFBP-2-overexpressing tumor cells, thus implicating IGFBP-2 in influencing intracellular peroxide levels. However, since transgenic mice with IGF-II or IGFBP-2 overexpression in the adrenal gland do not show an increased frequency of adrenal tumors, IGF-II or IGFBP-2 may act as progression factors but not as initiation factors in adrenocortical tumorigenesis.

Key words

IGF-I - IGF-II - IGF-I-receptor - IGFBP - Adrenal - Tumorigenesis

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Prof. Dr. med. M. M. Weber

Schwerpunkt Endokrinologie und Stoffwechselerkrankungen · I. Medizinische Klinik und Poliklinik · Johannes Gutenberg Universität Mainz

Langenbeckstraße 1 · 55131 Mainz · Germany

Phone: +49 (6131) 177260

Fax: +49 (6131) 175608

Email: MMWeber@uni-mainz.de