Differential expression of IGFBPs in Laron syndrome-derived lymphoblastoid cell lines: Potential correlation with reduced cancer incidence. (April 2018)

• Record Type: Journal Article
• Authors: Somri, Lina; Sarfstein, Rive; Lapkina-Gendler, Lena; Nagaraj, Karthik; Laron, Zvi; Bach, Leon A.; Werner, Haim
• Is Part Of: Growth hormone & IGF research. Volume 39(2018)
• Page Start: 6
• Page End: 12
• Publication Date: 2018-04
• Subjects: Insulin-like growth factor-1 (IGF-1) -- IGF binding protein (IGFBP) -- Laron syndrome -- Congenital IGF-1 deficiency -- Cancer protection; Growth regulators -- Periodicals; Growth -- Regulation -- Periodicals; Somatomedin -- Periodicals; Somatomedins -- Periodicals; Growth Hormone -- Periodicals; Growth Substances -- Periodicals; Croissance -- Régulation -- Périodiques; Croissance -- Régulateurs -- Périodiques; Somatotrophine -- Périodiques; Somatomédine -- Périodiques; Growth -- Regulation; Growth regulators; Electronic journals; Periodicals; Electronic journals; 612.4
• DOI: 10.1016/j.ghir.2017.11.004
• Languages: English
• ISSNs: 1096-6374

Abstract

Abstract: 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 H2 O2 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. Highlights: Epidemiological studies have shown that LS patients are protected from cancer. The hypothesis that IGFBPs are differentially expressed in LS was evaluated. IGFBP-3 was highly expressed in LS-derived lymphoblastoid cells. Levels of IGFBP-2, -5, and -6 were diminished in LS cells.