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dc.contributor.authorBasu, Alakananda
dc.creatorBlaydes, Rachel
dc.date.accessioned2019-08-22T19:52:48Z
dc.date.available2019-08-22T19:52:48Z
dc.date.issued2019-03-05T12:12:27-08:00
dc.date.submitted2019-02-11T08:06:53-08:00
dc.identifier.urihttps://hdl.handle.net/20.500.12503/27163
dc.description.abstractPurpose: Breast cancer is the most commonly diagnosed cancer in women with over 252,000 women in the United states getting diagnosed and more than 40,000 dying each year. Lack of cell death by apoptosis can cause cancer and contributes to chemoresistance. Protein kinase C (PKC) plays critical roles in cell survival and cell death. PKCη ,a member of the PKC family, is considered an anti-apoptotic kinase. We, therefore, examined if depletion of PKCη would enhance cellular sensitivity to chemotherapeutic agents by inducing apoptosis. Methods: Established breast cancer cell lines, such as MCF-7 cells (ATCC) were used in this study. Cells were transfected with non-targeting or target-specific siRNAs. The extent of gene knockdown was determined by Western blot analysis. The proteins from the cell extract were separated by SDS-PAGE and visualized using enhanced chemiluminescence detection kit. Cell proliferation was assessed using a clonogenic assay. The DNA damaging agent doxorubicin was used to induce apoptosis. The cleavage of PARP was used to monitor apoptosis. Cellular senescence was detected using SA-b-gal staining kit from Cell Signaling Technology. Results: Depletion of PKCη by siRNA decreased doxorubicin-induced apoptosis. PKCη knockdown increased the levels of the cell cycle inhibitor p27 and decreased the clonogenic survival of MCF-7 cells. Knockdown of PKCη caused upregulation of the cyclin-dependent kinase inhibitor p27. Depletion of p27 inhibited senescence and restored apoptosis in PKCη-depleted cells. Conclusion: Our results suggest that PKCη knockdown inhibits apoptosis by inducing p27-mediated senescence.
dc.language.isoen
dc.titleContrasting effects of protein kinase C-eta on apoptosis versus senescence
dc.typeposter
dc.type.materialtext
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