Journal Article

Sensitizing effects of cadmium on TNF-α- and TRAIL-mediated apoptosis of NIH3T3 cells with distinct expression patterns of p53

Byung Ju Kim, Mi-Suk Kim, Ki-Bae Kim, Ki-Woo Kim, Yeon-Mi Hong, In-Ki Kim, Han-Woong Lee and Yong-Keun Jung

in Carcinogenesis

Volume 23, issue 9, pages 1411-1417
Published in print September 2002 | ISSN: 0143-3334
Published online September 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.9.1411
Sensitizing effects of cadmium on TNF-α- and TRAIL-mediated apoptosis of NIH3T3 cells with distinct expression patterns of p53

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Tumor necrosis factor (TNF)-α and TNF-related apoptosis inducing ligand (TRAIL) share a common signaling pathway. Here we show a novel potentiating effect of cadmium on TNF-α- or TRAIL-mediated cell death via distinct signaling. TNF-α or TRAIL sensitized otherwise resistant NIH3T3 embryo fibroblast cells to death, when exposed to cadmium. The potentiating effects elicited by TNF-α or TRAIL on cell death were NF-κB- and SAPK/JNK-independent and were not diminished by the expression of Bcl-2. TNF-α potentiated the cadmium-induced accumulation of p53 but did not affect expression levels of Bax, Mdm2 and p21WAF/CIP. A similar pattern of p53 accumulation was also observed in Balbc/3T3 fibroblasts but not in human tumor cell lines, MCF7 and HeLa cells. The synergistic cell death evoked by TNF-α and cadmium was attenuated by transient expression of a dominant negative p53Val135 mutant in NIH3T3 cells and was not observed in p53(–/–) mouse embryo fibroblasts, indicating that p53 accumulation appears to contribute to cell death. In contrast, TRAIL did not further increase the cadmium-induced accumulation of p53 despite its potentiation effects on the cadmium-induced cell death. Expression of p53Val135 mutant did not reduce TRAIL- and cadmium-mediated cell death. Taken together, these results suggest that TNF-α and TRAIL potentiate the cadmium-mediated cell death via distinct p53 expression patterns.

Keywords: ROS, reactive oxygen species; TRAIL, TNF-related apoptosis inducing ligand; TNF-α, tumor necrosis factor-α

Journal Article.  5127 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.