title: Ionizing radiation activates expression of FOXO3a, Fas ligand, and Bim, and induces cell apoptosis.
abstract: Genotoxic stress such as ionizing radiation can induce DNA damage and promote cell-cycle arrest or apoptosis through either a p53-dependent or -independent pathway. Recently, members of the FOXO Forkhead transcription factor family have been implicated in playing a role in both DNA repair and apoptosis in mammalian cells that promoted us to examine the role of FOXO transcription factors in ionizing radiation-induced apoptosis. Here, we show that ionizing radiation can promote FOXO3a (FKHRL1) transcriptional activity and protein expression level, and induce nuclear translocation of FOXO3a in Saos2, a p53-null osteosarcoma cell line. Ionizing radiation stimulates expression of apoptosis-inducing proteins such as Fas ligand and the Bcl-2 interacting mediator of cell death (Bim) leading to cellular apoptosis. The observed upregulation of proapoptotic genes and apoptosis in cells without p53 in response to ionizing radiation suggests a novel p53-independent mechanism underlying ionizing radiation-induced apoptosis in cancer cells.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
authors.forename: Jer-Yen
authors.initials: JY
authors.lastname: Yang
authors.forename: Weiya
authors.initials: W
authors.lastname: Xia
authors.forename: Mickey C-T
authors.initials: MC
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D001859:Bone Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000528:radiation effects; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism* / Q000532:radiotherapy; D011401:Promoter Regions, Genetic; D021381:Protein Transport / Q000528:radiation effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011839:Radiation, Ionizing; D014158:Transcription, Genetic / Q000528:radiation effects; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C505661:FASLG protein, human; C499517:FOXO3 protein, human; D053222:Fas Ligand Protein; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D048069:Tumor Necrosis Factors; D016159:Tumor Suppressor Protein p53