Presentation Type
Oral/Paper Presentation
Abstract
Breast cancer (BC) is the most common cancer in women worldwide and the second leading cause of cancer-related deaths among females. BC arises from the uncontrolled proliferation of breast epithelial cells. A crucial gene associated with BC is the Breast Cancer Susceptibility Gene 2 (BRCA2), a tumor suppressor that aids in DNA repair. Proper BRCA2 function helps prevent BC. Our lab studied the cell cycle-dependent expression of BRCA2 revealing that its promoter exhibits bi-directional activity. During cell division, forward activity transcribes BRCA2, while in the resting phase, reverse activity transcribes ZAR2 (Zygote Arrest 1 Like). ZAR2, an RNA-binding protein with C4 zinc fingers, localizes to P-bodies, stress granules (SG), and paraspeckles, regulating RNA turnover. We found that BC cells with high ZAR2 levels exhibit greater stress tolerance and higher IC50 values for chemotherapy agents, including cisplatin, doxorubicin, and carboplatin. Thus, we hypothesize that ZAR2 overexpression in BC cells enhances chemotherapy resistance. To test this, we cloned ZAR2 into the pCMV-3XFLAG vector and transfected it into MDA-MB-231 and BT549 BC cell lines. We confirmed overexpression via Western blotting and immunofluorescence. Following ZAR2 manipulation, cells were then treated with doxorubicin and carboplatin, and viability was assessed using the PrestoBlue assay. Our results showed that ZAR2 overexpression reduced BC cell growth but increased survival under chemotherapy. Additionally, ZAR2 co-localizes with the stress granule marker G3BP1, suggesting a role in stress tolerance. These findings indicate that ZAR2, through stress granules, may contribute to chemotherapy resistance in BC.
Faculty Mentor
Smita Misra
Recommended Citation
Gerges, Maryam M. and Misra, Smita, "Impact of ZAR1L Expression on Drug Response in Breast Cancer Cells" (2025). Student Scholar Symposium. 87.
https://digitalcollections.lipscomb.edu/student_scholars_symposium/2025/Full_schedule/87
Included in
Impact of ZAR1L Expression on Drug Response in Breast Cancer Cells
Breast cancer (BC) is the most common cancer in women worldwide and the second leading cause of cancer-related deaths among females. BC arises from the uncontrolled proliferation of breast epithelial cells. A crucial gene associated with BC is the Breast Cancer Susceptibility Gene 2 (BRCA2), a tumor suppressor that aids in DNA repair. Proper BRCA2 function helps prevent BC. Our lab studied the cell cycle-dependent expression of BRCA2 revealing that its promoter exhibits bi-directional activity. During cell division, forward activity transcribes BRCA2, while in the resting phase, reverse activity transcribes ZAR2 (Zygote Arrest 1 Like). ZAR2, an RNA-binding protein with C4 zinc fingers, localizes to P-bodies, stress granules (SG), and paraspeckles, regulating RNA turnover. We found that BC cells with high ZAR2 levels exhibit greater stress tolerance and higher IC50 values for chemotherapy agents, including cisplatin, doxorubicin, and carboplatin. Thus, we hypothesize that ZAR2 overexpression in BC cells enhances chemotherapy resistance. To test this, we cloned ZAR2 into the pCMV-3XFLAG vector and transfected it into MDA-MB-231 and BT549 BC cell lines. We confirmed overexpression via Western blotting and immunofluorescence. Following ZAR2 manipulation, cells were then treated with doxorubicin and carboplatin, and viability was assessed using the PrestoBlue assay. Our results showed that ZAR2 overexpression reduced BC cell growth but increased survival under chemotherapy. Additionally, ZAR2 co-localizes with the stress granule marker G3BP1, suggesting a role in stress tolerance. These findings indicate that ZAR2, through stress granules, may contribute to chemotherapy resistance in BC.