Genome Expression Profiling of Holoclones Derived from Prostate Cancer
Yvonne Salley, Michael Gallagher, Salah Elbaruni, Paul Smyth, Cathy Spillane, Cara M Martin, William Watson, Orla M Sheils, John J O'Leary. Trinity College Dublin, Dublin, Ireland; Conway Institute, University College Dublin, Dublin, Ireland
Background: Prostate cancer is one of the five most prevalent malignancies in all male age groups worldwide. Prostate cancer is a heterogeneous disease and is the second most common cause of cancer resulting in male deaths caused by cancer and is the most commonly diagnosed cancer in Irish males. There are over 1500 new cases diagnosed every year in Ireland, the second leading cause of fatal cancer in Irish men (NCRI, 2010). Stem-like cells have been identified in several malignancies including prostate cancer and are thought to drive primary tumorigenesis through self-renewal and differentiation. Additionally, persistence of stem cells post-therapeutic intervention has been proposed as an explanation for metastasis and recurrence. Holoclones are a tightly packed clone of small cells generally thought to contain stem cells and progenitors. The aim of this study was to generate a whole genome expression profile of holoclone derived cell lineage in prostate cancer.
Design: In this study, holoclones were cultured using a high salt-soft agar assay for LNCaP (metastatic carcinoma) and PC-3 (non-metastatic adenocarcinoma) cell lines. Microarray analysis was carried out on cell lines and holoclone derived cells (n=4) and analysed by XRAY software using the criteria; FDR ≤ 0.05 and FC ± 2. Gene ontology of biological processes and pathways was generated with DAVID and PANTHER. Genes were selected and validated using a quantitative Real Time TaqMan® PCR method.
Results: Holoclones were generated from cell lines (LNCaP, PC-3) using a high salt-soft agar assay. PC-3 versus PC-3 holoclones demonstrated 228 significant differentially regulated genes and LNCap versus LNCaP holoclones demonstrated 44 significant differentially regulated genes and validations were confirmed.
Conclusions: Various genes were identified and validated which represent stemness, differentiation and EMT as well as numerous other biological processes involved in cancer progression establishment, progression and maintenance. These gene and their relevant functions have been found to be either significantly downregulated or upregulated specifically in the PC-3 and LNCaP holoclones indicating that these cells have specific expression profiles for each holoclone/founder set cancer stem cell holoclone potential.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 102, Tuesday Afternoon