Alterations in gene expression during radiation induced mitotic catastrophe in HeLa Hep2 cells

• Purpose: To explore kinetic changes in the gene expression profile during radiation induced mitotic catastrophes.Methods and Materials: We measured temporal global gene expression in HeLa Hep2 tumor cells using bead chip arrays (Illumina) following exposure to 5 Gy of ionizing radiation (60Co). Genes with less than a 2-fold change in expression and a p-value > 0.05 were discarded. Signaling pathways significantly altered following irradiation were explored using Metacore. Furthermore, biological responses linked to mitotic catastrophe including cell cycle arrests, anaphase bridge formation and centrosome amplification were analyzed and correlation to gene expression changes evaluated.Results: Following irradiation a G2-arrest was induced. This arrest was transient and cells entered mitosis before DNA damage was repaired causing anaphase bridge formation. Furthermore, radiation induced hyperamplification of centrosomes was observed. These phenotypical changes correlated well with the observed gene expression changes. At 6 h following irradiation the expression was changed only for a few genes including histone H2 and H4, essential for activation of a DNA-damage checkpoint. Striking changes appeared at later time-points. From 12-96 hours post irradiation a significant fraction of the genes with altered expression were found to be involved in cell cycle progression and its regulation. The significant changes were seen for genes important for several mitotic processes, and those involved in the G2- and spindle assembly checkpoints. Also centrosome associated genes displayed an increased expression. Furthermore, 96 hours after irradiation pathways involved in immune and inflammatory responses were significantly altered.Conclusions: This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be linked to the sequential steps observed in HeLa Hep2 cells during mitotic catastrophes. Therapeutic strategies employing these alterations might potentiate future therapy and enhance tumor cell killing.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Radiation; cell cycle checkpoint

cell death; mitotic catastrophe

gene expression

immunologi

Immunology

radiofysik

radiation physics

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