naa a22 4500 510763685 CHVBK 20180411083148.0 cr unu---uuuuu 180411e20130301xx s 000 0 eng 10.1007/s12094-012-0898-8 doi (NATIONALLICENCE)springer-10.1007/s12094-012-0898-8 Development and characterization of an isogenic cell line with a radioresistant phenotype [Elektronische Daten] [Lara de Llobet, Marta Baro, Agnès Figueras, Ignasi Modolell, Maria Da Silva, Purificación Muñoz, Arturo Navarro, Ricard Mesia, Josep Balart] Introduction: Radiation resistance is a major cause of death in cancer patients. Cancer cells react during radiotherapy by re-programming specific cell functions that may confer resistance to radiation. The understanding of this complex process is hindered due to the lack of appropriate study models. We describe an experimental development of a radioresistant isogenic cancer cell line, and its molecular characterization. Materials and methods: A431-cultured cells were irradiated for 7month until 85Gy. Then, a selected single cell was left to grow as stable A431-R cell line. Clonogenic assay was used to determine cell survival, the α and β parameters of the LQ model, and the mean inactivation dose. The DNA repair ability of cells was evaluated by pulsed-field electrophoresis method. Differential effect of fractionated radiation was ultimately tested in xenografts. Furthermore, we used a wound healing assay, Western blot for EGFR, AKT and ERK1/2 and ELISA test for vascular endothelial growth factor (VEGF) secretion. Finally we explored CD44 marker and cell cycle distribution. Results: The established A431-R cell line showed radiation resistance in clonogenic assays, repair of radiation-induced DNA fragmentation and xenografted tumours. The radiation resistance was associated with in vitro higher cell growth and migration, increased levels of former oncoproteins, and secretion of VEGF. Conclusions: In this model, the emergence of radiation resistance was associated with the acquisition of biological traits that support more aggressive behaviour of cancer cells. We have generated a model that will be useful for mechanistic studies and development of rational treatments against radiation resistance in cancer. Federación de Sociedades Españolas de Oncología (FESEO), 2012 Development of isogenic cell line model nationallicence Emergence of radiation resistance nationallicence Aggressive phenotype nationallicence de Llobet Lara Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut Baro Marta Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut Figueras Agnès Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut Modolell Ignasi Department of Radiophysics and Radioprotection, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Spain aut Da Silva Maria Cancer Biology and Epigenetics Laboratory, IDIBELL, L'Hospitalet de Llobregat, Spain aut Muñoz Purificación Cancer Biology and Epigenetics Laboratory, IDIBELL, L'Hospitalet de Llobregat, Spain aut Navarro Arturo Department of Radiation Oncology, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Spain aut Mesia Ricard Department of Medical Oncology, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Spain aut Balart Josep Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut Clinical and Translational Oncology Springer Milan 15/3(2013-03-01), 189-197 1699-048X 15:3<189 2013 15 12094 https://doi.org/10.1007/s12094-012-0898-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12094-012-0898-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- de Llobet Lara Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Baro Marta Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Figueras Agnès Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Modolell Ignasi Department of Radiophysics and Radioprotection, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Da Silva Maria Cancer Biology and Epigenetics Laboratory, IDIBELL, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Muñoz Purificación Cancer Biology and Epigenetics Laboratory, IDIBELL, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Navarro Arturo Department of Radiation Oncology, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Mesia Ricard Department of Medical Oncology, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 700 1- Balart Josep Translational Research Laboratory, Catalan Institute of Oncology - IDIBELL, Avda Gran Via de l'Hospitalet, 199-203, 08907, L'Hospitalet de Llobregat, Spain aut NATIONALLICENCE 773 0- Clinical and Translational Oncology Springer Milan 15/3(2013-03-01), 189-197 1699-048X 15:3<189 2013 15 12094 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer