The role of epithelial growth factors and insulin growth factors in the adrenal neoplasms

Abstract

Human fetal and adult adrenal gland express both insulin growth factor-1 (IGF-1) and IGF-2, their receptors (IGF-Rs) and a variety of specific IGF binding proteins suggesting their potential role in the regulation of adrenal growth and function. overexpression is essential for the growth of monoclonal lesions, such as large benign adenomas (ACA) and adrenocortical carcinomas (ACC) and has been found to contribute to tumorigenesis in Beckwith-Wiedemann syndrome. IGF-2 is the most highly expressed gene observed in more than 85% of ACCs. However, no significant differences in clinical, biological and transcriptomic traits were found between tumors with high and low expression of. On the contrary, the expression of , mediating the IGF-2 effects, was more discriminant between malignant (overexpression) and benign tumors. Data on the role of epithelial growth factor (EGF) and its receptor (EGF-R) in adrenocortical tumorigenesis are controversial. Several studies have shown overexpression in ACCs but not in benign ACAs, suggesting that could potentially be used as a marker for the differential diagnosis of ACAs and ACCs. Although, and animal studies provide promising results in the therapeutic role of IGF and EGF pathway inhibitors, the available data in humans are still not encouraging. Herein, we aim to present recent data on the role of IGF and EGF pathways in adrenal development and tumorigenesis and their potential implication in the treatment of the ACC, a rare malignancy with very poor prognosis.

The Association Between Thyroid Volume and Insulin Resistance in Patients with Non-Functional Adrenal Incidentaloma

“…In humans, fetal and adult adrenal gland has been shown to express insulin-like growth factor 1/2 (IGF-1/2) and its receptors, and these play a role in the growth and function of the adrenal gland. It has also been suggested that IGF-2 overexpression may cause benign adenomas and adrenocortical carcinomas (11). Hyperinsulinemia resulting from IR is reported to increase IGF-1 and IGF-1 receptors at the same time, by increasing IGF-1 and IGF-2 levels.…”

The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

“…The IGF-2 gene is located at 11p15 region that consists of a telomeric domain including the IGF-2 and H19 that might modulate IGF-2 expression and a centromeric domain including cyclin dependent kinase inhibitor (CDKNIC) involved in the G1/S phase of the cell cycle [ 11 ]. IGF-2 gene encodes IGF-2 protein and it is expressed by both fetal and adult adrenal glands and as a part of complex signaling system which plays an important role in normal growth and development, cell survival and proliferation as well as in malignant alteration [ 15 ]. IGF-2 overexpression was proven in more than 85% of ACCs although it is low or absent at the beginning of clonal proliferation [ 16 ].…”

“…Despite of its rarity, with global prevalence of 4–12 cases per million, adrenocortical carcinoma is the second, after anaplastic thyroid carcinoma, most lethal endocrine malignancy with 5-year overall survival being < 15% in advanced ACC [ 15 , 42 , 198 ]. The main obstacle is scarcity of effective and available treatment options [ 27 ].…”

Advanced Adrenocortical Carcinoma: Current Perspectives on Medical Treatment

“…These drugs potentially inhibit a cascade of signaling events that regulate cell growth and angiogenesis. Overexpression of tyrosine kinase receptors was documented in ACC particularly vascular endothelial growth factors and receptors (VEGF/VEGFR), epidermal growth factor and receptor (EGF/EGFR) and insulin-like growth factor (IGF) system comprised by the IGF ligands (IGF-1, IGF-2, insulin) and their cell surface receptors (IGF-1R, IGF-2R and insulin receptor) [23][24][25].…”

“…Signaling pathways such as PI3K/AKT/mTOR and MAPK (Ras/ Raf/MEK/ERK) resulting in cell survival, proliferation and tumor growth, are activated through IGF-1R and EGF-R in ACC [25].…”