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In the present study, we attempted to find a gene that was both induced by irradiation and associated with radioresistance in tumors. Using single-color oligo-microarrays, we analyzed the gene expression profiles of two murine squamous cell carcinomas, NR-S1, which is highly radioresistant, and SCCVII, which is radiosensitive, after irradiation with 137-Cs gamma rays or carbon ions. Candidate genes were those differentially regulated between NR-S1 and SCCVII after any kind of irradiation. Four genes, Efna1 (Ephrin-A1), Sprr1a (small proline-rich protein 1A), Srgap3 (SLIT-ROBO Rho GTPase activating protein 3) and Xrra1 [RIKEN 2 days neonate thymus thymic cells (NOD) cDNA clone E430023D08 3\u2032], were selected as candidate genes associated with radiotherapy-induced radioresistance. We focused on Efna1, which encodes a ligand for the Eph receptor tyrosine kinase known to be involved in the vascular endothelial growth factor (VEGF) pathway. We used immunohistochemical methods to detect expression of Ephrin-A1, VEGF, and the microvascular marker CD31 in radioresistant NR-S1 tumor cells. Ephrin-A1 was detected in the cytoplasm of NR-S1 tumor cells after irradiation, but not in SCCVII tumor cells. Irradiation of NR-S1 tumor cells also led to significant increases in microvascular density, and up-regulation of VEGF expression. Our results suggest that radiotherapy-induced changes in gene expression related with angiogenesis might also modulate microenvironment and influence responsiveness of tumors.<\/jats:p>","DOI":"10.3181\/0806-rm-189","type":"journal-article","created":{"date-parts":[[2008,11,7]],"date-time":"2008-11-07T21:49:14Z","timestamp":1226094554000},"page":"112-122","source":"Crossref","is-referenced-by-count":27,"title":["The Proangiogenic Factor Ephrin-A1 Is Up-Regulated in Radioresistant Murine Tumor by Irradiation"],"prefix":"10.3389","volume":"234","author":[{"given":"Kazunori","family":"Nojiri","sequence":"first","affiliation":[{"name":"Research Center for Charged Particle Therapy, National Institute of Radiological Sciences (NIRS), Chiba 263-8555, Japan; and Department of Gastroenterological Surgery, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Iwakawa","sequence":"additional","affiliation":[{"name":"Research Center for Charged Particle Therapy, National Institute of Radiological Sciences (NIRS), Chiba 263-8555, Japan; 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