Roles of protein kinase C in cell death and breast cancer
Author
Summary, in English
Previous reports have shown that PKCδ is a survival factor in several breast cancer cells. Here we show that Smac, a proapoptotic protein, associates with PKCδ in many different cancer cell lines. Furthermore, the PKCδ-Smac association was dissociated upon paclitaxel treatment. Upon PKC activation with TPA the PKCδ-Smac complex was stabilized and the paclitaxel-mediated dissociation and death was suppressed. The decreased cell death could potentially be caused by a competition between PKCδ and XIAP for Smac binding. We also show that activation of PKC sensitizes some breast cancer cell lines to a Smac mimetic called LBW242, a small molecule that mimic the effect of Smac. We found that the TPA+LBW242-mediated cell death was dependent on TPA-induced TNFα production. In addition the combination of TPA+LBW242 enables complex II formation and caspase-3 cleavage, a probable cause of the concomitant cell death observed.
Department/s
- Department of Translational Medicine
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2013
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2013:41
Full text
Document type
Dissertation
Publisher
Tumour Cell Biology, Department of Laboratory Medicine
Topic
- Cancer and Oncology
Keywords
- breast cancer
- protein kinase C
- apoptosis
- cell death
- Smac
- Smac mimetics
- IAP
- stanniocalcin-1
Status
Published
Supervisor
- Christer Larsson
- Annika Jögi
- Håkan Axelson
- Katarzyna Masoumi
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-87449-11-6
Defence date
26 April 2013
Defence time
09:15
Defence place
The main lecture hall, Jan Waldenströms gata 59, ingång 78, Skåne University Hospital, Malmö
Opponent
- Maria Shoshan (Associate Professor)