Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor(s)

Dr. Peeyush Lala

Abstract

Over-expression of inflammation associated enzyme cyclo-oxygenase (COX)-2 promotes breast cancer progression, metastasis and sustains cancer stem-like cells (SLCs) by activating prostaglandin E2 receptor EP4. Two COX-2 induced oncogenic miRNAs, miR-655 and miR-526b, target and down-regulate the cytoplasmic polyadenylation element binding protein (CPEB)-2. Hypothesis: Down-regulation of CPEB2 promotes an aggressive breast cancer phenotype through SLC induction and epithelial to mesenchymal transition (EMT). We found that high COX-2/miRNA expressing cell lines MDAMB231 and MCF7-COX-2 had significantly lower expression of CPEB2 than MCF7 cells (low COX-2/miRNA). CPEB2 knockdown in CPEB2-high MCF7 cell line resulted in increased migratory and invasive capacity in vitro. CPEB2 KD increased spheroid forming ability (SLC surrogate), expression of SLC markers (Nanog, ALDH1, SOX-2), and mesenchymal markers (Twist1, Snail), and decreased epithelial marker (E-Cadherin). Furthermore, treatment with COX-2 inhibitor and EP4 antagonist increased CPEB2 expression. Collectively, CPEB2 demonstrates anti-oncogenic functions and CPEB2 inhibition promotes an aggressive breast cancer phenotype.

Available for download on Saturday, September 30, 2017


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