Date of Graduation
5-2015
Document Type
Thesis (MS)
Program Affiliation
Biomedical Sciences
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Ronald A DePinho, MD
Committee Member
Laura Beretta, PhD
Committee Member
Elsa Renee Flores, PhD
Committee Member
Prahlad Ram, PhD
Committee Member
Hui-Kuan Lin, PhD
Committee Member
Alan Y Wang, PhD
Abstract
Poor prognosis of prostate cancer is correlated with rampant chromosomal copy number alterations, highlighting the potential function of genes with copy number gains and losses in driving prostate cancer progression. To identify putative genes promoting prostate cancer, an in vivo tumorigenesis screen was performed for 286 genes that are recurrently amplified and overexpressed in human prostate cancer. The transcription co-activator protein PYGO2 was identified as a major hit for further in vivo functional and clinical validation. Overexpression of PYGO2 could enhance primary tumor growth as well as local invasion to lymph nodes using AR-positive prostate cancer cell line LNCaP. PYGO2 may mediate its pro-tumor function through upregulation of genes including WNT2, ADAMTS2, IGFBP3 and downregulation of KISS1. Tissue microarray analysis indicated that PYGO2 upregulation was correlated with higher Gleason score in prostate cancer. Collectively, the results suggest PYGO2 as a potential prognostic marker as well as a therapeutic target. Additional functional characterization of PYGO2 in prostate cancer pathogenesis is warranted and ongoing.
Keywords
prostate cancer; genomic screen; PYGO2