Microarray analysis of radiation response genes in primary human fibroblasts

Enikö Kis, Tünde Szatmári, Márton Keszei, Róbert Farkas, O. Ésik, Katalin Lumniczky, A. Falus, G. Sáfrány

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Purpose: To identify radiation-induced early transcriptional responses in primary human fibroblasts and understand cellular pathways leading to damage correction. Methods and Materials: Primary human fibroblast cell lines were irradiated with 2 Gy γ-radiation and RNA isolated 2 h later. Radiation-induced transcriptional alterations were investigated with microarrays covering the entire human genome. Time- and dose dependent radiation responses were studied by quantitative real-time polymerase chain reaction (RT-PCR). Results: About 200 genes responded to ionizing radiation on the transcriptional level in primary human fibroblasts. The expression profile depended on individual genetic backgrounds. Thirty genes (28 up- and 2 down-regulated) responded to radiation in identical manner in all investigated cells. Twenty of these consensus radiation response genes were functionally categorized: most of them belong to the DNA damage response (GADD45A, BTG2, PCNA, IER5), regulation of cell cycle and cell proliferation (CDKN1A, PPM1D, SERTAD1, PLK2, PLK3, CYR61), programmed cell death (BBC3, TP53INP1) and signaling (SH2D2A, SLIC1, GDF15, THSD1) pathways. Four genes (SEL10, FDXR, CYP26B1, OR11A1) were annotated to other functional groups. Many of the consensus radiation response genes are regulated by, or regulate p53. Time- and dose-dependent expression profiles of selected consensus genes (CDKN1A, GADD45A, IER5, PLK3, CYR61) were investigated by quantitative RT-PCR. Transcriptional alterations depended on the applied dose, and on the time after irradiation. Conclusions: The data presented here could help in the better understanding of early radiation responses and the development of biomarkers to identify radiation susceptible individuals.

Original languageEnglish
Pages (from-to)1506-1514
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume66
Issue number5
DOIs
Publication statusPublished - Dec 1 2006

Fingerprint

fibroblasts
Microarray Analysis
genes
Fibroblasts
Radiation
radiation
Genes
polymerase chain reaction
Real-Time Polymerase Chain Reaction
dosage
Radiation Dosage
damage
Proliferating Cell Nuclear Antigen
Human Genome
genome
Ionizing Radiation
biomarkers
apoptosis
profiles
DNA Damage

Keywords

  • Fibroblast
  • Gene expression
  • Microarray
  • Radiation response

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Microarray analysis of radiation response genes in primary human fibroblasts. / Kis, Enikö; Szatmári, Tünde; Keszei, Márton; Farkas, Róbert; Ésik, O.; Lumniczky, Katalin; Falus, A.; Sáfrány, G.

In: International Journal of Radiation Oncology Biology Physics, Vol. 66, No. 5, 01.12.2006, p. 1506-1514.

Research output: Contribution to journalArticle

Kis, Enikö ; Szatmári, Tünde ; Keszei, Márton ; Farkas, Róbert ; Ésik, O. ; Lumniczky, Katalin ; Falus, A. ; Sáfrány, G. / Microarray analysis of radiation response genes in primary human fibroblasts. In: International Journal of Radiation Oncology Biology Physics. 2006 ; Vol. 66, No. 5. pp. 1506-1514.
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T1 - Microarray analysis of radiation response genes in primary human fibroblasts

AU - Kis, Enikö

AU - Szatmári, Tünde

AU - Keszei, Márton

AU - Farkas, Róbert

AU - Ésik, O.

AU - Lumniczky, Katalin

AU - Falus, A.

AU - Sáfrány, G.

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AB - Purpose: To identify radiation-induced early transcriptional responses in primary human fibroblasts and understand cellular pathways leading to damage correction. Methods and Materials: Primary human fibroblast cell lines were irradiated with 2 Gy γ-radiation and RNA isolated 2 h later. Radiation-induced transcriptional alterations were investigated with microarrays covering the entire human genome. Time- and dose dependent radiation responses were studied by quantitative real-time polymerase chain reaction (RT-PCR). Results: About 200 genes responded to ionizing radiation on the transcriptional level in primary human fibroblasts. The expression profile depended on individual genetic backgrounds. Thirty genes (28 up- and 2 down-regulated) responded to radiation in identical manner in all investigated cells. Twenty of these consensus radiation response genes were functionally categorized: most of them belong to the DNA damage response (GADD45A, BTG2, PCNA, IER5), regulation of cell cycle and cell proliferation (CDKN1A, PPM1D, SERTAD1, PLK2, PLK3, CYR61), programmed cell death (BBC3, TP53INP1) and signaling (SH2D2A, SLIC1, GDF15, THSD1) pathways. Four genes (SEL10, FDXR, CYP26B1, OR11A1) were annotated to other functional groups. Many of the consensus radiation response genes are regulated by, or regulate p53. Time- and dose-dependent expression profiles of selected consensus genes (CDKN1A, GADD45A, IER5, PLK3, CYR61) were investigated by quantitative RT-PCR. Transcriptional alterations depended on the applied dose, and on the time after irradiation. Conclusions: The data presented here could help in the better understanding of early radiation responses and the development of biomarkers to identify radiation susceptible individuals.

KW - Fibroblast

KW - Gene expression

KW - Microarray

KW - Radiation response

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