title: Identification of signaling pathways associated with cancer protection in Laron syndrome.
abstract: The growth hormone (GH)-insulin-like growth factor-1 (IGF1) pathway emerged in recent years as a critical player in cancer biology. Enhanced expression or activation of specific components of the GH-IGF1 axis, including the IGF1 receptor (IGF1R), is consistently associated with a transformed phenotype. Recent epidemiological studies have shown that patients with Laron syndrome (LS), the best-characterized entity among the congenital IGF1 deficiencies, seem to be protected from cancer development. To identify IGF1-dependent genes and signaling pathways associated with cancer protection in LS, we conducted a genome-wide analysis using immortalized lymphoblastoid cells derived from LS patients and healthy controls of the same gender, age range, and ethnic origin. Our analyses identified a collection of genes that are either over- or under-represented in LS-derived lymphoblastoids. Gene differential expression occurs in several gene families, including cell cycle, metabolic control, cytokine-cytokine receptor interaction, Jak-STAT signaling, and PI3K-AKT signaling. Major differences between LS and healthy controls were also noticed in pathways associated with cell cycle distribution, apoptosis, and autophagy. Our results highlight the key role of the GH-IGF1 axis in the initiation and progression of cancer. Furthermore, data are consistent with the concept that homozygous congenital IGF1 deficiency may confer protection against future tumor development.
authors.affiliation: Department of Human Molecular Genetics and BiochemistrySackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Lena
authors.initials: L
authors.lastname: Lapkina-Gendler
authors.affiliation: Department of Human Molecular Genetics and BiochemistrySackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Rotem
authors.affiliation: Bioinformatics UnitGeorge Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.affiliation: Department of Human Molecular Genetics and BiochemistrySackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Yoran Institute for Human Genome ResearchTel Aviv University, Tel Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Gurwitz
authors.affiliation: Department of Human Molecular Genetics and BiochemistrySackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rive
authors.initials: R
authors.lastname: Sarfstein
authors.affiliation: Endocrine and Diabetes Research UnitSchneider Children's Medical Center, Petah Tikva, Israel.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Laron
authors.affiliation: Department of Human Molecular Genetics and BiochemistrySackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Yoran Institute for Human Genome ResearchTel Aviv University, Tel Aviv, Israel hwerner@post.tau.ac.il.
authors.forename: Haim
authors.initials: H
authors.lastname: Werner
mesh_terms: D000328:Adult; D017209:Apoptosis; D001343:Autophagy; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D046150:Laron Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D059467:Transcriptome
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Laron syndrome; cancer protection; dwarfism; growth hormone receptor; insulin-like growth factor-1