title: Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation.
abstract: Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range.
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul, 132703, Korea.
authors.forename: Hyun Soon
authors.initials: HS
authors.lastname: Bang
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul, 132703, Korea.
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Choi
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul, 132703, Korea.
authors.forename: Cha Soon
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul, 132703, Korea ijms@chollian.net.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Choi
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology / Q000528:radiation effects; D002454:Cell Differentiation / Q000235:genetics* / Q000528:radiation effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation / Q000528:radiation effects; D005720:Gamma Rays; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D013997:Time Factors; D015854:Up-Regulation / Q000528:radiation effects
keywords: carcinogenesis; cell line; gene expression; radiation; thyroid gland