title: Genetic alterations following ionizing radiation in human ovarian cancer-derived endothelial cells.
abstract: Recent studies have focused on the role of endothelial cells during tumor radiotherapy, and the majority of studies have found that the rate of endothelial cell apoptosis determines the response of the tumor to ionizing radiation treatment. However, gene expression changes in human ovarian cancer-derived endothelial cells in response to X-ray radiation remains poorly understood. The present study was conducted to investigate the radiation-induced gene alterations in human ovarian cancer-derived endothelial cells and to provide novel potential targets for combined anti-angiogenesis and radiation therapy for the treatment of human ovarian cancer. Ovarian cancer-derived endothelial cells, which were harvested from six human ovarian epithelial carcinomas prior to and 4 h after 400 cGy X-ray irradiation, were analyzed using cDNA microarray technology. Significant genes were selected to corroborate the microarray experiments using a quantitative polymerase chain reaction (qPCR). A total of 28 genes common to all the cDNA microarray results were identified, of which 22 genes were found to be consistently upregulated or downregulated. Thirteen genes were upregulated persistently and nine genes downregulated persistently following irradiation with 400 cGy X-ray in comparison with the matched group. The majority of the significantly altered genes (≥2-fold change in expression) were found to have a role in vasculogenesis, cell cycle regulation, inflammation and the immune response, cell growth and apoptosis, nicotinamide metabolism, cell signaling, chemokines and cell adhesion. Eight randomly selected genes were corroborated using qPCR technology. Radiation-induced gene alterations in ovarian cancer-derived endothelial cells and gene-related pathways were associated with vasculogenesis and the radiosensitivity of human ovarian cancer, and may provide promising biomarkers for radiation and anti-angiogenesis treatments against ovarian carcinoma.
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
authors.forename: Xiugui
authors.initials: X
authors.lastname: Sheng
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D002869:Chromosome Aberrations / Q000528:radiation effects*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D009389:Neovascularization, Pathologic / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D015203:Reproducibility of Results; D015398:Signal Transduction