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Thioredoxin overexpression in HT‐1080 cells induced cellular senescence and sensitization to gamma radiation
Author(s) -
Byun Hee Sun,
Cho Eun Wie,
Kim Jin Sik,
Moon Myung Sook,
Yum Jung Joo,
Kim Kug Chan,
Kim In Gyu
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.06.023
Subject(s) - senescence , microbiology and biotechnology , biology , kinase , cell growth , g2 m dna damage checkpoint , cell cycle , dna damage , cancer research , cell cycle checkpoint , cell , genetics , dna
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 H 2 O 2 or paraquat. But these cells were significantly sensitive to ionizing radiation, showing an abrogation of the G 2 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.