Identification of signaling pathways associated with cancer protection in Laron syndrome

Autor: Rive Sarfstein, Zvi Laron, Lena Lapkina-Gendler, David Gurwitz, Itai Rotem, Metsada Pasmanik-Chor, Haim Werner
Rok vydání: 2016
Předmět:
Adult
endocrine system
Cancer Research
medicine.medical_specialty
Sp1 Transcription Factor
Endocrinology
Diabetes and Metabolism
Apoptosis
030209 endocrinology & metabolism
Growth hormone receptor
Biology
Cell Line
Receptor
IGF Type 1
03 medical and health sciences
0302 clinical medicine
Endocrinology
Neoplasms
Internal medicine
Autophagy
Laron syndrome
medicine
Humans
Insulin-Like Growth Factor I
Extracellular Signal-Regulated MAP Kinases
Cell Proliferation
Insulin-like growth factor 1 receptor
Cell Cycle
PTEN Phosphohydrolase
Cancer
Receptors
Somatomedin
Middle Aged
Cell cycle
medicine.disease
Phenotype
Laron Syndrome
Oncology
030220 oncology & carcinogenesis
Metabolic control analysis
Cancer research
Female
Signal transduction
Transcriptome
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Endocrine-Related Cancer. 23:399-410
ISSN: 1479-6821
1351-0088
DOI: 10.1530/erc-16-0054
Popis: 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.
Databáze: OpenAIRE
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