GENE EXPRESSION PROFILING OF CD133+ PROSTATE CANCER STEM CELLS INDUCED FROM PC3 CARCINOMA CELL LINE CULTURES

摘要

According to the stem cell model of cancer progression, the disease emerges through mutations and epigenetic modifications that disrupt normal function in adult stem cells. These cancer stem cells (CSCs) constitute a very small subset of the tumor and are responsible for establishing and maintaining the disease. The identification of potential therapeutic targets that are differentially expressed in the normal and malignant stem cell populations has been limited by the lack of suitable in vitro experimental models. We report the implementation of a custom cell culture protocol for the enrichment of the CD133~+ CSC population from PC3 carcinoma cells. When analyzed by flow cytometry, using anti-CD 133 (293C3) labeled antibodies we observed that this side population becomes significantly enriched (up to 5.6% positive events) as compared to standard protocols (0.2%). We further characterized both CD133~+ and CD133~- fractions using novel gene expression-profiling technology. Functional annotation of differentially expressed gene patterns reveals, up-regulation of pathways comprising several genes associated with cell fate as well as DNA repair mechanisms, cell cycle regulation, inhibition of differentiation and metastasis.