Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Peeyush K. Lala

Abstract

Our laboratory previously established that aberrant expression of cyclo-oxygenase (COX)-2 promotes breast cancer progression and metastasis via multiple mechanisms, including stem-like cell (SLC) induction, owing to activation of the prostaglandin E2 receptor EP4. COX-2 expression was linked to up-regulation of miRNA-526b. We hypothesized that miR-526b is regulated by EP4 activity, and that miR-526b supports breast cancer progression and induction of SLCs. Using stably miR-526b transfected MCF-7 and SKBR-3 cells in functional assays, including tumorsphere formation in vitro and lung colony formation in vivo, we observed enhanced migration, invasion, proliferation, tumorsphere formation, and in vivo tumorigenecity compared to controls. EP4 receptor activation and inhibition resulted in respective increases or decreases in miR-526b expression in PKA and PI3K-AKT dependent manners. We conclude that miR-526b promotes breast cancer progression and SLC induction, is up-regulated by EP4, and holds promise as a biomarker for monitoring and personalizing breast cancer treatment.


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