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

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalRadiation Research
Volume160
Issue number2
DOIs
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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