Analysis of the Regulation and Function of CIP2A to Identify Candidate Biomarkers for Prostate Cancer
Master's in Molecular Pathology and Immunology
Graduate School of Biomedical Sciences
School of Osteopathic Medicine
Medical Diagnostic Laboratories and their Affiliates of Hamilton, New Jersey
Lyndi Rice, PhD
Jason Trama, PhD
Grant Gallagher, PhD
Protein Phosphatase 2; Oncogenes; Biomarkers; Prostatic Neoplasms; Phosphorylation
Cancer Biology | Cell Biology | Genetic Processes | Laboratory and Basic Science Research | Male Urogenital Diseases | Medical Genetics | Medical Molecular Biology | Medicine and Health Sciences | Neoplasms
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.
Savoly, Diana, "Analysis of the Regulation and Function of CIP2A to Identify Candidate Biomarkers for Prostate Cancer" (2014). Graduate School of Biomedical Sciences Theses and Dissertations. 13.
Cancer Biology Commons, Cell Biology Commons, Genetic Processes Commons, Laboratory and Basic Science Research Commons, Male Urogenital Diseases Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Neoplasms Commons
Additional advisor/Committee member: Salvatore Caradonna, PhD