Date Approved

4-2014

Document Type

Thesis

Degree Name

Master's in Molecular Pathology and Immunology

Department

Graduate School of Biomedical Sciences

College

School of Osteopathic Medicine

First Advisor

Lyndi Rice, PhD

Committee Member 1

Jason Trama, PhD

Committee Member 2

Grant Gallagher, PhD

Committee Member 3

Salvatore Caradonna, PhD

Subject(s)

Protein Phosphatase 2, Oncogenes, Biomarkers, Prostatic Neoplasms, Phosphorylation

Disciplines

Cancer Biology | Cell Biology | Genetic Processes | Laboratory and Basic Science Research | Male Urogenital Diseases | Medical Genetics | Medical Molecular Biology | Medicine and Health Sciences | Neoplasms

Abstract

Protein Phosphatase 2A (PP2A) is a tumor suppressor involved in the regulation of several signaling pathways and the cell cycle. PP2A becomes inactivated by several inhibitors, including Cancerous Inhibitor of PP2A (CIP2A). CIP2A has been identified as an oncogene, which is over-expressed in cancers and inhibits PP2A through direct interaction. CIP2A is recognized as a biomarker for cancer; however, it is not cancer-specific. Therefore, we identified and examined the use of CIP2A-regulated proteins as potential biomarkers in prostate cancer to better diagnose prostate cancer in patients. Currently, Prostate Specific Antigen (PSA) is widely used to detect prostate cancer; however, it is not a reliable diagnostic marker and early diagnosis is paramount to the successful treatment of prostate cancer. Thus, we identified six potentially CIP2A-regulated proteins, five which were confirmed to be CIP2A-regulated.

We also created CIP2A phospho-mutants on the C-terminus of CIP2A, which was shown to interact with PP2A through yeast-two hybrid studies. We used these mutants to carry out several functional assays to determine if they altered CIP2A’s cancerous phenotype. We completed several functional assays including; cell proliferation, wound healing, apoptosis, invasion and migration assays. We also asked if CIP2A phosphorylation-state affected PP2A-binding. Our results suggest that the phosphorylation status of CIP2A residues Y626 and S638 affect CIP2A function.

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