Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors.
J Clin Endocrinol Metab
; 83(5): 1713-20, 1998 May.
Article
em En
| MEDLINE
| ID: mdl-9589681
ABSTRACT
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.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like II
/
Neoplasias do Córtex Suprarrenal
/
Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article