Glioblastoma multiforme (GBM) is the deadliest form of primary brain tumor that affects adults. The median survival rate for GBM from the time of diagnosis is about 12-15 months, with less than 10% survival beyond 5 years. Although surgery, radiation and chemotherapy are considered the most effective therapeutic options for this type of cancer, and despite the advancements made in these fields, prognoses have remained very poor. The activator protein-1 (AP-1) is a transcription factor that mediates many cellular responses ranging from cell proliferation and differentiation to tumorigeneses and cell death. Importantly, it has been found that AP-1 regulates different processes involved in brain cancer progression including proliferation, invasion, migration and metastasis. CAPER (Co-activator of AP-1 and ER) is an AP-1 co-activator that was recently found to be involved in human breast cancer progression. Nevertheless, the role of CAPER in human brain cancer pathogenesis remains unknown. Here, we propose that CAPER could serve as a novel therapeutic target for GBM. In fact, our results demonstrate that CAPER is significantly upregulated in patient glioma tissue samples. We also show that lentiviral-mediated knockdown of CAPER expression in a glioma cell line was able to decrease cell numbers by 60%. This effect was attributed to the induction of G2/M phase cell cycle arrest, mitochondrial damage, apoptosis and cell death. Importantly, knockdown of CAPER expression also hindered the development of tumors in nude mice.
|Commitee:||Harvison, Peter, Suryanarayanan, Asha|
|School:||University of the Sciences in Philadelphia|
|Department:||Pharmacology and Toxicology|
|School Location:||United States -- Pennsylvania|
|Source:||MAI 57/02M(E), Masters Abstracts International|
|Keywords:||Animal models, Apoptusis, Astrocytoma, Brain cancer, CAPER, Co-activator of AP-1 and ER, Oncology|
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