Journal of Nippon Medical School: Vol.71 No.3 page.172

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ArticleTitle Effect of Ionizing Irradiation on Human Esophageal Cancer Cell Lines by cDNA Microarray Gene Expression Analysis

AuthorList Hideki Bo^1,2, Mohammad Ghazizadeh¹, Hajime Shimizu¹, Yuji Kurihara², Seiko Egawa¹, Yukichi Moriyama², Takashi Tajiri³, Oichi Kawanami¹

Affiliation ¹Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School
²Center for Digestive Diseases, Nippon Medical School Second Hospital
³Surgery for Organ Function and Biological Regulation, Nippon Medical School, Graduate School of Medicine

Language EN

Volume 71

Issue 3

Year 2004

Page 172-180

Received January 9, 2004

Accepted January 19, 2004

Keywords esophageal squamous cell carcinoma (ESCC), cell line, radiation, gene expression, cDNA microarray

Abstract
To provide new insights into the molecular mechanisms underlying the effect of irradiation on esophageal squamous cell carcinomas (ESCCs), we used a cDNA microarray screening of more than 4,000 genes with known functions to identify genes involved in the early response to ionizing irradiation. Two human ESCC cell lines, one each of well (TE-1) and poorly (TE-2) differentiated phenotypes were screened. Subconfluent cells of each phenotype were treated with single doses of 2.0 Gy or 8.0 Gy irradiations. After a 15 min incubation time-point, the cells were collected and analyzed. Compared with non-irradiated cells, many genes revealed at least 2-fold upregulation or downregulation at both doses in well or poorly differentiated ESCC cells. The common upregulated genes in well and poorly differentiated cell types at both irradiation doses included SCYA5, CYP51, SMARCD2, COX6C, MAPK8, FOS, UBE2M, RPL6, PDGFRL, TRAF2, TNFAIP6, ITGB4, GSTM3, and SP3 and common downregulated genes involved NFIL3, SMARCA2, CAPZA1, MetAP2, CITED2, DAP3, MGAT2, ATRX, CIAO1, and STAT6. Several of these genes were novel and not previously known to be associated with irradiation. Functional annotations of the modulated genes suggested that at the molecular level, irradiation appears to induce a regularizing balance in ESCC cell function. The genes modulated in the early response to irradiation may be useful in our understanding of the molecular basis of radiotherapy and in developing strategies to augment its effect or establish novel less hazardous alternative adjuvant therapies.

Correspondence to Mohammad Ghazizadeh, MD, Ph D, Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, 211-8533, Japan
ciem@nms.ac.jp

ArticleTitle	Effect of Ionizing Irradiation on Human Esophageal Cancer Cell Lines by cDNA Microarray Gene Expression Analysis
AuthorList	Hideki Bo^1,2, Mohammad Ghazizadeh¹, Hajime Shimizu¹, Yuji Kurihara², Seiko Egawa¹, Yukichi Moriyama², Takashi Tajiri³, Oichi Kawanami¹
Affiliation	¹Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School ²Center for Digestive Diseases, Nippon Medical School Second Hospital ³Surgery for Organ Function and Biological Regulation, Nippon Medical School, Graduate School of Medicine
Language	EN
Volume	71
Issue	3
Year	2004
Page	172-180
Received	January 9, 2004
Accepted	January 19, 2004
Keywords	esophageal squamous cell carcinoma (ESCC), cell line, radiation, gene expression, cDNA microarray
Abstract	To provide new insights into the molecular mechanisms underlying the effect of irradiation on esophageal squamous cell carcinomas (ESCCs), we used a cDNA microarray screening of more than 4,000 genes with known functions to identify genes involved in the early response to ionizing irradiation. Two human ESCC cell lines, one each of well (TE-1) and poorly (TE-2) differentiated phenotypes were screened. Subconfluent cells of each phenotype were treated with single doses of 2.0 Gy or 8.0 Gy irradiations. After a 15 min incubation time-point, the cells were collected and analyzed. Compared with non-irradiated cells, many genes revealed at least 2-fold upregulation or downregulation at both doses in well or poorly differentiated ESCC cells. The common upregulated genes in well and poorly differentiated cell types at both irradiation doses included SCYA5, CYP51, SMARCD2, COX6C, MAPK8, FOS, UBE2M, RPL6, PDGFRL, TRAF2, TNFAIP6, ITGB4, GSTM3, and SP3 and common downregulated genes involved NFIL3, SMARCA2, CAPZA1, MetAP2, CITED2, DAP3, MGAT2, ATRX, CIAO1, and STAT6. Several of these genes were novel and not previously known to be associated with irradiation. Functional annotations of the modulated genes suggested that at the molecular level, irradiation appears to induce a regularizing balance in ESCC cell function. The genes modulated in the early response to irradiation may be useful in our understanding of the molecular basis of radiotherapy and in developing strategies to augment its effect or establish novel less hazardous alternative adjuvant therapies.
Correspondence to	Mohammad Ghazizadeh, MD, Ph D, Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, 211-8533, Japan ciem@nms.ac.jp