Thioredoxin overexpression in HT-1080 cells induced cellular senescence and sensitization to gamma radiation
- 6 July 2005
- journal article
- Published by Wiley in FEBS Letters
- Vol. 579 (19) , 4055-4062
- https://doi.org/10.1016/j.febslet.2005.06.023
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 arrestKeywords
This publication has 22 references indexed in Scilit:
- Mouse Development and Cell Proliferation in the Absence of D-CyclinsCell, 2004
- Intravenous Administration of Thioredoxin Decreases Brain Damage Following Transient Focal Cerebral Ischemia in MiceAntioxidants and Redox Signaling, 2004
- α-Difluoromethylornithine, ornithine decarboxylase inhibitor, antagonizes H2O2-induced cytotoxicity in HL-60 leukemia cells: Regulation of iron-dependent lysosomal damageCell Biology and Toxicology, 2003
- Reduced Hepatic Tumor Incidence in Cyclin G1–Deficient MiceHepatology, 2003
- One More Reason to Get Arrested (in G1)Cell Cycle, 2002
- Overexpression of Human Thioredoxin in Transgenic Mice Controls Oxidative Stress and Life SpanAntioxidants and Redox Signaling, 2002
- A Redox-Inactive Thioredoxin Reduces Growth and Enhances Apoptosis in WEHI7.2 CellsBiochemical and Biophysical Research Communications, 2000
- Extension of Life-Span by Overexpression of Superoxide Dismutase and Catalase in Drosophila melanogasterScience, 1994
- Cloning and sequencing of cDNAs encoding the actin cross‐liking protein transgelin defines a new family of actin‐associated proteinsCell Motility, 1994
- Reduction of paraquat toxicity by superoxide dismutaseLife Sciences, 1974