Insulin and Insulin-Like Growth Factor-1 (IGF-1) Inhibit Repair of Potentially Lethal Radiation Damage and Chromosome Aberrations and Alter DNA Repair Kinetics in Plateau-Phase A549 Cells

1995 ◽  
Vol 143 (2) ◽  
pp. 165 ◽  
Author(s):  
Vikram R. Jayanth ◽  
Charles A. Belfi ◽  
Alan R. Swick ◽  
Marie E. Varnes
Keyword(s):  
Dna Repair ◽  
Growth Factor ◽  
Radiation Damage ◽  
Chromosome Aberrations ◽  
A549 Cells ◽  
Insulin Like Growth Factor ◽  
Plateau Phase

scholarly journals Role of the Insulin-Like Growth Factor I/Insulin Receptor Substrate 1 Axis in Rad51 Trafficking and DNA Repair by Homologous Recombination

2003 ◽  
Vol 23 (21) ◽  
pp. 7510-7524 ◽  
Author(s):  
Joanna Trojanek ◽  
Thu Ho ◽  
Luis Del Valle ◽  
Michal Nowicki ◽  
Jin Ying Wang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Growth Factor ◽  
Homologous Recombination ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Insulin Like Growth Factor ◽  
Insulin Receptor Substrate 1 ◽  
Factor I ◽  
Igf I

ABSTRACT The receptor for insulin-like growth factor I (IGF-IR) controls normal and pathological growth of cells. DNA repair pathways represent an unexplored target through which the IGF-IR signaling system might support pathological growth leading to cellular transformation. However, this study demonstrates that IGF-I stimulation supports homologous recombination-directed DNA repair (HRR). This effect involves an interaction between Rad51 and the major IGF-IR signaling molecule, insulin receptor substrate 1 (IRS-1). The binding occurs within the cytoplasm, engages the N-terminal domain of IRS-1, and is attenuated by IGF-I-mediated IRS-1 tyrosine phosphorylation. In the absence of IGF-I stimulation, or if mutated IGF-IR fails to phosphorylate IRS-1, localization of Rad51 to the sites of damaged DNA is diminished. These results point to a direct role of IRS-1 in HRR and suggest a novel role for the IGF-IR/IRS-1 axis in supporting the stability of the genome.

scholarly journals Insulin-Like Growth Factor-1–Mediated DNA Repair in Irradiated Salivary Glands Is Sirtuin-1 Dependent

2016 ◽  
Vol 96 (2) ◽  
pp. 225-232 ◽  
Author(s):  
S. Meyer ◽  
A.M. Chibly ◽  
R. Burd ◽  
K.H. Limesand
Keyword(s):  
Dna Repair ◽  
Salivary Gland ◽  
Growth Factor ◽  
Head And Neck ◽  
Sirtuin 1 ◽  
Insulin Like Growth Factor ◽  
Parotid Glands ◽  
Protein Levels ◽  
Wide Range ◽  
Head And Neck Radiation

Ionizing radiation is one of the most common cancer treatments; however, the treatment leads to a wide range of debilitating side effects. In patients with head and neck cancer (HNC), the surrounding normal salivary gland is extremely sensitive to therapeutic radiation, and damage to this tissue results in various oral complications and decreased quality of life (QOL). In the current study, mice treated with targeted head and neck radiation showed a significant increase in double-stranded breaks (DSB) in the DNA of parotid salivary gland cells immediately after treatment, and this remained elevated 3 h posttreatment. In contrast, mice pretreated with insulin-like growth factor-1 (IGF-1) showed resolution of the same amount of initial DNA damage by 3 h posttreatment. At acute time points (30 min to 2 h), irradiated parotid glands had significantly decreased levels of the histone deactylase Sirtuin-1 (SirT-1) which has been previously shown to function in DNA repair. Pretreatment with IGF-1 increased SirT-1 protein levels and increased deacetylation of SirT-1 targets involved in DNA repair. Pharmacological inhibition of SirT-1 activity decreased the IGF-1–mediated resolution of DSB. These data suggest that IGF-1 promotes DNA repair in irradiated parotid glands through the maintenance and activation of SirT-1.

scholarly journals Silencing of the type 1 insulin-like growth factor receptor increases the sensitivity to apoptosis and inhibits invasion in human lung adenocarcinoma A549 cells

2007 ◽  
Vol 12 (4) ◽  
Author(s):  
Zhiyuan Ma ◽  
Aiqiang Dong ◽  
Minjian Kong ◽  
Jianfang Qian
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Human Lung ◽  
A549 Cells ◽  
Growth Factor Receptor ◽  
Insulin Like Growth Factor ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

AbstractThe type 1 insulin-like growth factor receptor (IGF-1R), which is over-expressed or activated in many human cancers, including lung cancer, mediates cancer cell proliferation and metastasis. Several studies indicate that blocking IGF-1R expression can inhibit tumor cell proliferation and metastasis. In this study, inhibition of the endogenous IGF-1R by recombinant adenoviruses encoding short hairpin RNAs against IGF-1R was found to significantly suppress IGF-1R expression, arrest the cell cycle, enhance the apoptotic response, and inhibit proliferation, adhesion, invasion and migration in A549 cells. Moreover, silencing IGF-1R decreases the expression of invasive-related genes including matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-plasminogen activator (u-PA), and the phosphorylation of Akt and ERK1/2. These results suggest that the silencing of IGF-1R has the potential to be an effective cancer gene therapy strategy for human lung cancer.

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