title: Thioredoxin overexpression in HT-1080 cells induced cellular senescence and sensitization to gamma radiation.
abstract: An increment of thioredoxin-1 (TRX) is observed in many human primary cancers and appears to contribute to an increase of cell growth and a resistance to chemotherapy. On the contrary, when TRX was overexpressed in the HT-1080 fibrosarcoma cells, the cell growth was retarded and chromosomal polyploidy and cellular senescence were induced. TRX-overexpression made HT-1080 cells resistant to an oxidative stress caused by H2O2 or paraquat. But these cells were significantly sensitive to ionizing radiation, showing an abrogation of the G2 checkpoint. Their DNA contents were twice of the controls and they expressed typical senescence markers. Their expression levels of p53 and cyclin-dependent kinase inhibitors (CDKI) were about 2-3-fold higher than the control. Nevertheless, cyclin D1 and D3, which are negatively regulated by CDKIs, were also increased. Overall, in HT-1080 cells the TRX-overexpression created a state of cellular senescence caused by a simultaneous stimulation of the mitogen-activated pathways and an inhibition of the cyclin-dependent kinases, which is known as a hypermitogenic arrest.
authors: Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600, Republic of Korea.
authors: Hee Sun
authors: HS
authors: Byun
authors: Eun Wie
authors: EW
authors: Cho
authors: Jin Sik
authors: JS
authors: Kim
authors: Myung Sook
authors: MS
authors: Moon
authors: Jung Joo
authors: JJ
authors: Yum
authors: Kug Chan
authors: KC
authors: Kim
authors: In Gyu
authors: IG
authors: Kim
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D008856:Microscopy, Fluorescence; D016877:Oxidants / Q000494:pharmacology; D011123:Polyploidy; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D016877:Oxidants; D013879:Thioredoxins