Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 280, Issue 3, Pages 883-891Publisher
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.4209
Keywords
tumor necrosis factor-alpha; protein kinase C; caspases; apoptosis; NF-kappa B; breast cancer cells; PKC epsilon
Categories
Funding
- NCI NIH HHS [CA71727] Funding Source: Medline
Ask authors/readers for more resources
We have compared several breast cancer cell lines that differ in their responsiveness to TNF to determine the involvement of PKC isozymes in regulating sensitivity of breast cancer cells to TNF. While MCF-7 and BT-20 cells were responsive to TNF without any metabolic inhibitors, CAMA-1 and SKBR-3 cells responded to TNF in the presence of cycloheximide; MDA-MB-231 and Hs578t cells were resistant to TNF even in the presence of cycloheximide. Bisindolylmaleimide (BIM), an inhibitor of PKC, either alone (MCF-7 and BT-20) or in combination with cycloheximide enhanced sensitivity of these cells to TNF. The PKC isozyme profile of MCF-7 cells was similar to BT-20 cells and that of CAMA-1 cells was similar to SKBR-3 cells. MCF-7, BT-20 and MDA-MB-231 cells that were most responsive to BIM-mediated sensitization to TNF contained relatively high level of PKC epsilon and proteolytic cleavage of PKC epsilon correlated with TNF-induced cell death. BIM did not inhibit NF-kappaB activation by TNF but caused activation of caspases and enhanced cleavage of PKC delta and -epsilon. These results suggest that proteolytic cleavage of PKC epsilon may be associated with PKC inhibitor mediated sensitization of breast cancer cells to TNF. (C) 2001 Academic Press.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available