Differential expression of IGFBPs in Laron syndrome-derived lymphoblastoid cell lines: Potential correlation with reduced cancer incidence
| Autor: | Lena Lapkina-Gendler, Haim Werner, Zvi Laron, Lina Somri, Karthik Nagaraj, Rive Sarfstein, Leon A. Bach |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism Apoptosis Growth hormone receptor Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Endocrinology Neoplasms Internal medicine medicine Laron syndrome Humans Lymphocytes Gene Lymphoblast Middle Aged medicine.disease Phenotype Laron Syndrome Insulin-Like Growth Factor Binding Proteins Oxidative Stress 030104 developmental biology Case-Control Studies 030220 oncology & carcinogenesis Female Signal transduction Oxidative stress |
| Zdroj: | Growth Hormone & IGF Research. 39:6-12 |
| ISSN: | 1096-6374 |
| DOI: | 10.1016/j.ghir.2017.11.004 |
| Popis: | Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is a growth disorder that results from mutation of the GH-receptor (GHR) gene leading to congenital insulin-like growth factor-1 (IGF-1) deficiency. Recent epidemiological studies have shown that LS patients are protected from cancer development. Genome-wide profiling identified genes and signaling pathways that are differentially represented in LS patients, and that may contribute to cancer protection. The present study was aimed at evaluating the hypothesis that IGF binding proteins (IGFBPs) are differentially expressed in LS, most probably as a result of low circulating levels of IGF-1. Furthermore, we postulated that IGFBPs might be differentially regulated by oxidative stress in this condition and, therefore, may contribute to cancer evasion. Our results show that IGFBP-3, which is predominantly protective, was highly expressed in LS-derived lymphoblastoid cells in comparison to control cells from the same ethnic group. On the other hand, levels of IGFBP-2, -4, -5, and -6 were diminished in LS patients, as demonstrated by RQ-PCR, Western immunoblots and confocal immunofluorescence. In addition, our data provide evidence for a pattern of IGFBP response to H2O2 treatment that might be associated with distinct expression of apoptosis markers (BCL2, pro-caspase-9, pro-caspase-3) in LS. In summary, differential expression of specific IGFBPs in LS might be correlated with cellular mechanisms underlying cancer protection and, probably, additional phenotypes due to congenital IGF-1 deficiency. |
| Databáze: | OpenAIRE |
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