CaM-DR5 binding regulates DR5-mediated caspase signaling in TN and ER+ breast cancer cells.
Primary Faculty Mentor’s Name
Yuhua Song
Proposal Track
Student
Session Format
Poster
Abstract
Estrogen receptor positive (ER+) breast cancers or triple negative breast cancers (TNBC) are breast cancer subtypes (J Clin Oncol: 27,1153-1154, 2009). Approximately 10 to 20 percent of breast cancers are TNBC (Cancer Research: 1, 20-21, 2011). TNBC and anti-hormone drug resistant ER+ breast cancers are aggressive breast cancers with poor clinical outcome TRA-8 is a monoclonal antibody used to induce apoptosis in human TNBC cells. ER+ and TNBC cells have a range of in vitro sensitivity to TRA-8 mediated cytotoxicity (Nature medicine: 7, 954-960, 2001). TRA-8 induces death receptor 5 (DR5) activation via formation of death inducing signaling complex (DISC). DR5-activated DISC initiates apoptotic signaling, through caspase cleavage and activation. Calmodulin (CaM) is overexpressed in breast cancer (J Clin Oncol: 4, 994-1012, 1986, Cancer research: 42, 2571-2574, 1982). Previously, our lab has shown CaM binds to DR5 and functions in DR5 mediated DISC formation in ER+ and TNBC cells. TRA-8 sensitive ER-positive ZR-75-1 breast cancer cells or TNBC MDA-MB-231 will be respectively, untreated, treated with 10 µm TFP (CaM antagonist) or 2 mm EGTA (Ca+2 chelator) only, treated with TRA-8 for 3 hours, pretreated with 10 µm TFP or 2 mm EGTA for 30 minutes then TRA-8 for 3 hours. Cell lysates were analyzed by western blot. Results have shown for both TNBC MDA-MB-231 and ER-positive ZR-75-1 cells, TFP or EGTA treatment decreased DR5-activated caspase-8, caspase-3, and PARP cleavage, but not caspase-9 cleavage, demonstrating that CaM-DR5 binding regulates DR5-mediated caspase cleavage.
Keywords
TRA-8, death receptor 5, calmodulin, breast cancer cells, apoptotic signaling
Award Consideration
1
Location
Concourse and Atrium
Presentation Year
2015
Start Date
11-7-2015 10:10 AM
End Date
11-7-2015 11:20 AM
Publication Type and Release Option
Presentation (Open Access)
Recommended Citation
Everette, Dynisty Y., "CaM-DR5 binding regulates DR5-mediated caspase signaling in TN and ER+ breast cancer cells." (2015). Georgia Undergraduate Research Conference (2014-2015). 83.
https://digitalcommons.georgiasouthern.edu/gurc/2015/2015/83
CaM-DR5 binding regulates DR5-mediated caspase signaling in TN and ER+ breast cancer cells.
Concourse and Atrium
Estrogen receptor positive (ER+) breast cancers or triple negative breast cancers (TNBC) are breast cancer subtypes (J Clin Oncol: 27,1153-1154, 2009). Approximately 10 to 20 percent of breast cancers are TNBC (Cancer Research: 1, 20-21, 2011). TNBC and anti-hormone drug resistant ER+ breast cancers are aggressive breast cancers with poor clinical outcome TRA-8 is a monoclonal antibody used to induce apoptosis in human TNBC cells. ER+ and TNBC cells have a range of in vitro sensitivity to TRA-8 mediated cytotoxicity (Nature medicine: 7, 954-960, 2001). TRA-8 induces death receptor 5 (DR5) activation via formation of death inducing signaling complex (DISC). DR5-activated DISC initiates apoptotic signaling, through caspase cleavage and activation. Calmodulin (CaM) is overexpressed in breast cancer (J Clin Oncol: 4, 994-1012, 1986, Cancer research: 42, 2571-2574, 1982). Previously, our lab has shown CaM binds to DR5 and functions in DR5 mediated DISC formation in ER+ and TNBC cells. TRA-8 sensitive ER-positive ZR-75-1 breast cancer cells or TNBC MDA-MB-231 will be respectively, untreated, treated with 10 µm TFP (CaM antagonist) or 2 mm EGTA (Ca+2 chelator) only, treated with TRA-8 for 3 hours, pretreated with 10 µm TFP or 2 mm EGTA for 30 minutes then TRA-8 for 3 hours. Cell lysates were analyzed by western blot. Results have shown for both TNBC MDA-MB-231 and ER-positive ZR-75-1 cells, TFP or EGTA treatment decreased DR5-activated caspase-8, caspase-3, and PARP cleavage, but not caspase-9 cleavage, demonstrating that CaM-DR5 binding regulates DR5-mediated caspase cleavage.
