Project description:Subset of adult prostate basal cells and fetal prostate epithelial cells have enhanced tubule-initiating capability in vivo. Features associated with this process may be co-opted in cancer cells We used microarrays to contrast gene expression profiles of fetal and adult tubule-initiating cells compared to basal and luminal epithelial cells that can be isolated from bening prostate tissue specimens.
Project description:MicroRNAs (miRNAs) are non-protein-coding small RNAs in the size range 19–25 nucleotides (nt) that are cleaved from 70-100 nt hairpin pre-miRNA precursors.MiRNAs bind to complementary sequences in the 3′-untranslated regions of their target mRNAs and induce mRNA degradation or translational repression. Recent intensive studies have revealed that miRNAs play important roles in a large number of biological processes, including cellular differentiation, proliferation and death. These wide-ranging biological roles suggest that miRNAs may be involved in cancer development. MiRNAs regulate a variety of biological processes, including developmental timing, signal transduction, cell growth, and cell death.
Project description:A subpopulation of prostate luminal epithelial cells has been previously reported to be sufficient to regenerate prostatic architecture following consecutive rounds of androgen deprivation/repletion. This functional characteristic suggest prostate luminal epithelial cells as the putative cell-of-origin for castration-resistant prostate cancer - which more notizable fenotype is the lack of response to androgen deprivation thereapy. We used microarrays to profile the androgen-induced transcripts in luminal prostate epithelial cells involved in a cycle of prostate regression/regeneration in Hoxb13-rtTA|TetO-H2BGFP transgenic mice.
Project description:A greater understanding of cell signaling events that occur within the prostate cancer tumor microenvironment (TME), for example between cancer-associated fibroblasts (CAFs) and prostate epithelial or cancer cells, may identify novel biomarkers and more effective therapeutic strategies for this disease. To address this, we used cell-type specific labelling with amino acid precursors (CTAP) to define cell type-specific phosphoproteomic changes that occur when prostate epithelial cells are co-cultured with normal patient-derived prostate fibroblasts (NPFs) versus matched CAFs.
Project description:The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development and RNA processing. Consistent with their expression profiles, basal cells functionally exhibit intrinsic stem-like and proneural properties with enhanced ribosome RNA (rRNA) transcription activity. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. Therefore, we link the cell-type specific gene signatures to subtypes of prostate cancer development, and identify genes associated with patient clinical outcome.
Project description:To conduct comparative transcriptomic analyses on normal or malignant prostate epithelial cells in response to tissue contextual changes, we cultured immortalized prostate epithelial cells or prostate cancer cells as cell monolayers or three-dimensional organoids and profiled their transcriptomes in respective culture contexts.