Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors - PubMed (original) (raw)

Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors

N Boulle et al. J Clin Endocrinol Metab. 1998 May.

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.

PubMed Disclaimer

Cited by

Etoposide Triggers Cellular Senescence by Inducing Multiple Centrosomes and Primary Cilia in Adrenocortical Tumor Cells.
Teng YN, Chang HC, Chao YY, Cheng HL, Lien WC, Wang CY. Teng YN, et al. Cells. 2021 Jun 11;10(6):1466. doi: 10.3390/cells10061466. Cells. 2021. PMID: 34208028 Free PMC article.
Review paper: origin and molecular pathology of adrenocortical neoplasms.
Bielinska M, Parviainen H, Kiiveri S, Heikinheimo M, Wilson DB. Bielinska M, et al. Vet Pathol. 2009 Mar;46(2):194-210. doi: 10.1354/vp.46-2-194. Vet Pathol. 2009. PMID: 19261630 Free PMC article. Review.
Type I insulin-like growth factor receptor signaling in hematological malignancies.
Vishwamitra D, George SK, Shi P, Kaseb AO, Amin HM. Vishwamitra D, et al. Oncotarget. 2017 Jan 3;8(1):1814-1844. doi: 10.18632/oncotarget.12123. Oncotarget. 2017. PMID: 27661006 Free PMC article. Review.
IGFBP2: integrative hub of developmental and oncogenic signaling network.
Li T, Forbes ME, Fuller GN, Li J, Yang X, Zhang W. Li T, et al. Oncogene. 2020 Mar;39(11):2243-2257. doi: 10.1038/s41388-020-1154-2. Epub 2020 Jan 10. Oncogene. 2020. PMID: 31925333 Free PMC article. Review.
IGF2 role in adrenocortical carcinoma biology.
Pereira SS, Monteiro MP, Costa MM, Moreira Â, Alves MG, Oliveira PF, Jarak I, Pignatelli D. Pereira SS, et al. Endocrine. 2019 Nov;66(2):326-337. doi: 10.1007/s12020-019-02033-5. Epub 2019 Aug 4. Endocrine. 2019. PMID: 31378849 Free PMC article.

Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors - PubMed (original) (raw)