Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors.
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.
Boulle
N
N
Laboratoire d'Explorations Fonctionnelles Endocriniennes, Hôpital Trousseau, Paris, France.
Logié
A
A
Gicquel
C
C
Perin
L
L
Le Bouc
Y
Y
D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000737:chemistry / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018976:Insulin-Like Growth Factor Binding Protein 6; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II