Alterations in tumour necrosis factor signaling pathways associated with cytotoxicity and resistance to taxanes in tumour cells.

ABSTRACT: The taxanes are widely used in the treatment of breast and other cancers. While their cytotoxicity has been attributed to the induction of cell cycle arrest in mitosis through the stabilization of microtubules, we found that docetaxel promotes soluble tumor necrosis factor alpha (TNF-alpha production in MCF-7 breast tumor cells. TNF-alpha induces apoptotic cell death in a variety of cell types by binding to one of its receptors (TNFR1) which promotes death-inducing signaling complex (DISC) formation. Consistent with this view, we also report that selection of MCF-7 cells for survival in increasing concentrations of paclitaxel or docetaxel results in selection of drug-resistant variants that are resistant to TNF-alpha cytotoxicity. MCF-7 cells selected to 3-5 nM docetaxel produced >30-f

ORGANISM(S): Homo sapiens

SUBMITTER: baoqing guo 

PROVIDER: E-GEOD-26129 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress