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1 August 2003 Reduction of 14-3-3 Proteins Correlates with Increased Sensitivity to Killing of Human Lung Cancer Cells by Ionizing Radiation
Wenqing Qi, Jesse D. Martinez
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Abstract

Qi, W. and Martinez J. D. Reduction of 14-3-3 Proteins Correlates with Increased Sensitivity to Killing of Human Lung Cancer Cells by Ionizing Radiation. Radiat. Res. 160, 217–223 (2003).

The 14-3-3 proteins have a wide range of ligands and are involved in a variety of biological pathways. Importantly, 14-3-3 proteins are known to be overexpressed in some human lung cancers, suggesting that they may play a role in tumorigenesis. Here we examined 14-3-3 expression in several lung cancer-derived cell lines and found that four of the seven 14-3-3 isoforms, β, ϵ, θ and ζ, were highly expressed in both lung cancer cell lines and normal lung fibroblasts. Two isoforms, σ and γ, were present only at very low levels. Immunoprecipitation data showed 14-3-3ζ could bind to CDC25C in irradiated A549 cells, and suppression of 14-3-3ζ in A549 cells with antisense resulted in a decrease in CDC25C localization in cytoplasm and CDC2 phosphorylation on Tyr15. As a consequence, CDC2 activity remained elevated which resulted in release from radiation-induced G2/M-phase arrest. Moreover, 16% 14-3-3ζ antisense-transfected cells underwent apoptosis when exposed to 10 Gy ionizing radiation. These data indicate that 14-3-3ζ is involved in G2 checkpoint activation and that inhibition of 14-3-3 may be a useful approach to sensitize human lung cancers to ionizing radiation.

Wenqing Qi and Jesse D. Martinez "Reduction of 14-3-3 Proteins Correlates with Increased Sensitivity to Killing of Human Lung Cancer Cells by Ionizing Radiation," Radiation Research 160(2), 217-223, (1 August 2003). https://doi.org/10.1667/RR3038
Received: 11 November 2002; Accepted: 1 April 2003; Published: 1 August 2003
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