Theres Lindgren1, Torgny Stigbrand1, Lennart Johansson2, Katrine Riklund3, David Eriksson4. 1. Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden. 2. Department of Radiation Sciences, Radiation Physics, Umeå University, Umeå, Sweden. 3. Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden. 4. Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden david.eriksson@climi.umu.se.
Abstract
AIM: To explore kinetic changes in the gene expression profile during radiation-induced mitotic catastrophes. MATERIALS AND METHODS: Gene expression changes were measured in HPV-infected HeLa Hep2 tumor cells following exposure to 5 Gy of ionizing radiation ((60)Co). Signaling pathways were explored and correlated to the biological responses linked to mitotic catastrophe. RESULTS: Following irradiation a transient G2-arrest was induced. Anaphase bridge formation and centrosome hyperamplification was observed. These phenotypical changes correlated well with the observed gene expression changes. Genes with altered expression were found to be involved in mitotic processes as well as G2- and spindle assembly checkpoints. Also centrosome-associated genes displayed an increased expression. CONCLUSION: This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be correlated to the events of mitotic catastrophe in HeLa Hep2 cells. Therapeutic strategies modulating these alterations might potentiate future therapy and enhance tumor cell killing. Copyright
AIM: To explore kinetic changes in the gene expression profile during radiation-induced mitotic catastrophes. MATERIALS AND METHODS: Gene expression changes were measured in HPV-infected HeLa Hep2 tumor cells following exposure to 5 Gy of ionizing radiation ((60)Co). Signaling pathways were explored and correlated to the biological responses linked to mitotic catastrophe. RESULTS: Following irradiation a transient G2-arrest was induced. Anaphase bridge formation and centrosome hyperamplification was observed. These phenotypical changes correlated well with the observed gene expression changes. Genes with altered expression were found to be involved in mitotic processes as well as G2- and spindle assembly checkpoints. Also centrosome-associated genes displayed an increased expression. CONCLUSION: This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be correlated to the events of mitotic catastrophe in HeLa Hep2 cells. Therapeutic strategies modulating these alterations might potentiate future therapy and enhance tumor cell killing. Copyright
Authors: Vasileios Askoxylakis; Gino B Ferraro; David P Kodack; Mark Badeaux; Ram C Shankaraiah; Giorgio Seano; Jonas Kloepper; Trupti Vardam; John D Martin; Kamila Naxerova; Divya Bezwada; Xiaolong Qi; Martin K Selig; Elena Brachtel; Dan G Duda; Peigen Huang; Dai Fukumura; Jeffrey A Engelman; Rakesh K Jain Journal: J Natl Cancer Inst Date: 2015-11-07 Impact factor: 13.506