All ETDs from UAB

Advisory Committee Chair

Etty N Benveniste

Advisory Committee Members

Vithal Ghanta

Rosa Serra

Document Type

Thesis

Date of Award

2014

Degree Name by School

Master of Science (MS) College of Arts and Sciences

Abstract

Breast cancer is the most common malignancy in women worldwide, and it remains a major cause of mortality, thus necessitating further advancements in treatment. In breast cancer, numerous cell signaling pathways are aberrantly activated in order to produce the myriad phenotypes associated with malignancy; such pathways include the PI3K/Akt/mTOR, NF-κB and JAK/STAT cascades. These pathways are highly interconnected, but one prominent lateral enhancer of each is the remarkably promiscuous kinase CK2. CK2 expression has been shown to be elevated in human cancer, thus implicating it in tumorigenesis through its effects on known oncogenic signaling cascades. In this study, differential aberrant expression of CK2 subunits is identified in human breast samples from the TCGA and METABRIC datasets. Additionally, two specific small molecule inhibitors of CK2, CX-4945 and TBB, were used to examine the role of CK2 in two human breast cancer cell lines, MDA-MB-231 and MCF-7 cells. We show that CK2 inhibition attenuates constitutive PI3K/Akt/mTOR, NF-κB and JAK/STAT3 activation as well as inducible NF-κB and JAK/STAT activation and downstream transcriptional activity. Finally, CX-4945 treatment caused a range of phenotypic changes in these breast cancer cell lines, including decreased viability, cell cycle arrest, apoptosis and loss of migratory capacity. Overall, these results demonstrate the huge potential of CK2 as a clinical target in breast cancer.

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