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Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation

Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor (GH-R) gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies....

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Autores principales: Werner, Haim, Sarfstein, Rive, Nagaraj, Karthik, Laron, Zvi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696416/
https://www.ncbi.nlm.nih.gov/pubmed/33182502
http://dx.doi.org/10.3390/cells9112446
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author Werner, Haim
Sarfstein, Rive
Nagaraj, Karthik
Laron, Zvi
author_facet Werner, Haim
Sarfstein, Rive
Nagaraj, Karthik
Laron, Zvi
author_sort Werner, Haim
collection PubMed
description Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor (GH-R) gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies. Epidemiological analyses have shown that LS patients do not develop cancer, whereas heterozygous family members have a cancer prevalence similar to the general population. To identify genes and signaling pathways differentially represented in LS that may help delineate a biochemical and molecular basis for cancer protection, we have recently conducted a genome-wide profiling of LS patients. Studies were based on our collection of Epstein–Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from LS patients, relatives and healthy controls. Bioinformatic analyses identified differences in gene expression in several pathways, including apoptosis, metabolic control, cytokine biology, Jak-STAT and PI3K-AKT signaling, etc. Genes involved in the control of cell cycle, motility, growth and oncogenic transformation are, in general, down-regulated in LS. These genetic events seem to have a major impact on the biological properties of LS cells, including proliferation, apoptosis, response to oxidative stress, etc. Furthermore, genomic analyses allowed us to identify novel IGF1 downstream target genes that have not been previously linked to the IGF1 signaling pathway. In summary, by ‘mining’ genomic data from LS patients, we were able to generate clinically-relevant information in oncology and, potentially, related disciplines.
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spelling pubmed-76964162020-11-29 Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation Werner, Haim Sarfstein, Rive Nagaraj, Karthik Laron, Zvi Cells Review Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor (GH-R) gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies. Epidemiological analyses have shown that LS patients do not develop cancer, whereas heterozygous family members have a cancer prevalence similar to the general population. To identify genes and signaling pathways differentially represented in LS that may help delineate a biochemical and molecular basis for cancer protection, we have recently conducted a genome-wide profiling of LS patients. Studies were based on our collection of Epstein–Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from LS patients, relatives and healthy controls. Bioinformatic analyses identified differences in gene expression in several pathways, including apoptosis, metabolic control, cytokine biology, Jak-STAT and PI3K-AKT signaling, etc. Genes involved in the control of cell cycle, motility, growth and oncogenic transformation are, in general, down-regulated in LS. These genetic events seem to have a major impact on the biological properties of LS cells, including proliferation, apoptosis, response to oxidative stress, etc. Furthermore, genomic analyses allowed us to identify novel IGF1 downstream target genes that have not been previously linked to the IGF1 signaling pathway. In summary, by ‘mining’ genomic data from LS patients, we were able to generate clinically-relevant information in oncology and, potentially, related disciplines. MDPI 2020-11-09 /pmc/articles/PMC7696416/ /pubmed/33182502 http://dx.doi.org/10.3390/cells9112446 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Werner, Haim
Sarfstein, Rive
Nagaraj, Karthik
Laron, Zvi
Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation
title Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation
title_full Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation
title_fullStr Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation
title_full_unstemmed Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation
title_short Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation
title_sort laron syndrome research paves the way for new insights in oncological investigation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696416/
https://www.ncbi.nlm.nih.gov/pubmed/33182502
http://dx.doi.org/10.3390/cells9112446
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