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Molecular & Cellular Toxicology

, Volume 8, Issue 1, pp 9–18 | Cite as

Genome-wide microarray investigation of molecular targets and signaling networks in response to high-LET neutron in in vivo-mimic spheroid of human carcinoma

  • Jee Young Kwon
  • Jung Min Kim
  • Young Hoon Ji
  • Young Rok SeoEmail author
Original Paper

Abstract

Although conventional clinical treatment with low LET (linear energy transfer) including gamma-ray and X-ray has been widely used for radiotherapy in various cancers, however, ineffective outcomes occur due to radioresistance caused by p53 mutation. High LET has become alternative since it is able to induce apoptosis regardless of p53 status. Indeed, the molecular mechanisms toward high LET have been suggested. Nevertheless, most studies have been done in monolayer culture system which cannot promptly represent solid tumor microenvironment. Here we applied in vivo mimic 3D spheroid to conduct microarray-based genomic expression and molecular signaling pathway analyses under neutron irradiation. As a result, 3D spheroid system was achieved using thermorevesible gel system. An effective apoptosis-inducible dose of neutron was determined by Acridine Orange (AO) staining in 3D spheroid. Differentially expressed genes in both unique and common responses to neutron were identified in the 3D spheroid compared to the monolayer cells. Total 95 and 169 genes were notably altered at transcription level toward neutron in monolayer and 3D spheroid system, respectively. Based on microarray data, putative apoptosis signaling was depicted using Pathway Studio software. In 3D-in vivo mimic model, the molecular networks interacted with ITGB1, MAP4K4, PAPPA, and SGK1 might be suggested as plausible molecular pathways. In conclusion, we demonstrate novel molecular signaling and corresponding targets of in vitro solid tumor following high LET exposure. This result might provide critical clues for clarification of neutron-induced apoptosis mechanism.

Keywords

Apoptosis Microarray Neutron irradiation Radioresistance Spheroid 

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Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Netherlands 2012

Authors and Affiliations

  • Jee Young Kwon
    • 1
    • 2
    • 3
  • Jung Min Kim
    • 4
  • Young Hoon Ji
    • 5
    • 6
  • Young Rok Seo
    • 1
    • 2
    Email author
  1. 1.Department of Life ScienceDongguk University-SeoulSeoulKorea
  2. 2.Institute of Environmental Medicine for Green ChemistryDongguk University-SeoulSeoulKorea
  3. 3.Department of Biomedical Science, School of MedicineKyung Hee UniversitySeoulKorea
  4. 4.NAR Center & Institute of Traditional Medicine and Bioscience of Daejeon UniversityDaejeonKorea
  5. 5.Division of Radiation Cancer Research, Research Institute of Radiological and Medical SciencesKorea Institute of Radiological and Medical SciencesSeoulKorea
  6. 6.Department of Radiation Oncology, Korea Cancer Center HospitalKorea Institute of Radiological and Medical SciencesSeoulKorea

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