Apoptosis mechanisms in human breast cancer cells

1. Research group name/project:
Apoptosis mechanisms in human breast cancer cells

2. Group leader and some key members (incl. from other depts./inst.):
Øystein Fodstad (prof, MD), Terje Lund (PhD), Yvonne Andersson (PhD), Olav Engebraaten (MD, PhD)

3. Home address on the internet:
http://radium.no/fodstad

4. Department/Institute:
Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

5. Main aim of research group:
To clarify molecular mechanisms and intracellular signalling pathways involved in cell death of cancer cells induced by immunotoxins or garlic extracts. We focus on activation of different protein kinases and effects on mitochondria caused by bcl-2 family proteins and activation of caspases.

6. Some important recent results (with a few key references):
The immunotoxin (IT) we are working with consists of a targeting moiety (antibody), which binds to a highly expressed antigen on breast cancer cells, linked to the bacterial toxin Pseudomonas Exotoxin A. The IT altered the protein-generating machinary but also induced apoptosis of the cancer cells. We have recently showed a rapid activation of the caspase cascade and a down-regulation of the anti-apoptotic Mcl-1 caused by IT-treatment (Andersson et al submitted Int.J.Cancer, 2003)

7. Methods in current use:
Cell culturing and fractionation, western blotting, immunoprecipitation, cytotoxic assays, DNA fragmentation analysis, flow cytometry

8. Available equipment:
Western blotting apparatus, 2-D-electrophoresis apparatus and microscopy equipment

9. Tentative name of possible collaborative project(s):
Changes in expression of and modifications of bcl-2-family proteins during apoptosis

10. Some key search words:
Human breast cancer, immunotoxin, garlic, apoptosis, protein synthesis inhibition, mitochondria