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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 5 1713-1720
Copyright © 1998 by The Endocrine Society

Original Studies

Increased Levels of Insulin-Like Growth Factor II (IGF-II) and IGF-Binding Protein-2 Are Associated with Malignancy in Sporadic Adrenocortical Tumors1

Nathalie Boulle, Armelle Logié, Christine Gicquel, Laurence Perin and Yves Le Bouc

Laboratoire d’Explorations Fonctionnelles Endocriniennes, Hôpital Trousseau, 75012 Paris, France

Address all correspondence and requests for reprints to: Dr. Nathalie Boulle, Laboratoire d’Explorations Fonctionnelles Endocriniennes, Hôpital Trousseau, 26 avenue Arnold Netter, 75012 Paris, France.

In adrenocortical tumors, malignancy is strongly associated with insulin-like growth factor II (IGF-II) gene overexpression and abnormalities at the 11p15 locus, suggesting a role for this growth factor in adrenocortical tumorigenesis. To further investigate this role, the IGF/IGF-binding protein (IGFBP) system was analyzed in 18 adrenocortical tumors, classified into 2 groups on the basis of their IGF-II messenger ribonucleic acid (mRNA) content (group 1, normal IGF-II mRNA content, mostly benign tumors; group 2, high IGF-II mRNA content, mostly malignant tumors).

Group 2 tumors contained 10 times more IGF-II protein than group 1 tumors or normal adrenal tissue (P < 0.001), indicating efficient translation of IGF-II mRNA in malignant tumors. Western ligand blotting detected various functional IGFBPs in normal adrenocortical glands and tumors: a doublet of 39–42 kDa identified by immunoblotting as IGFBP-3, a band at 32 kDa, and bands at 29–30 and 24 kDa. Total IGFBP-3 protein levels were similar in the two groups of tumors. By contrast, malignant tumors differed from benign ones by specific expression of the 32-kDa IGFBP. Immunoblotting identified this 32-kDa band together with a proteolytic fragment of 25 kDa as IGFBP-2, and quantitative analysis showed significantly higher levels of total IGFBP-2 in malignant tumors than in benign tumors (P < 0.001). Despite enhanced levels of IGBP-2 protein in malignant tumors, no increase in IGFBP-2 mRNA levels was detected, suggesting post-transcriptional regulation of this IGFBP.

These results confirm the major role of IGF-II in adrenocortical tumorigenesis and suggest that IGFBP-2 may be a regulator of IGF-II proliferative effects in this tumor system.




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