Expression Profiling of Holoclone and Non-Holoclone Derived Cell Lineage in Prostate Cancer.
Yvonne M Salley, Michael F Gallagher, Paul C Smyth, Cara M Martin, Orla M Sheils, John J O'Leary. University of Dublin, Trinity College, Dublin, Ireland
Background: Prostate cancer is a heterogeneous disease and is the second most common cause of cancer resulting in male deaths caused by cancer. 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 an 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 following 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. Both PC-3 and LNCaP holoclones displayed a unique stemness expression signature.
Conclusions: Microarray analysis demonstrated that holoclone derived cells display significant stemness gene expression when compared to the founder cell lines. Analysis also indicated different stemness characteristics between PC-3 and LNCaP holoclones. Future work will consist of further characterisation of holoclone cells. Acknowledgements: Prostate Cancer Research Consortium.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Monday, February 28, 2011 1:00 PM
Poster Session II # 237, Monday Afternoon