Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA278856 | ENA |
REPOSITORIES: ENA
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Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells. Transcriptional analysis of 10 uncultured prostatic basal and luminal populations from either the benign or malignant prostate tissue of 8 human prostate cancer patients by high-throughput RNA-seq
2016-06-01 | E-GEOD-82071 | biostudies-arrayexpress
Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells.
2016-06-01 | GSE82071 | GEO
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. Human total RNA profiles of 3 pairs of benign prostatic basal and luminal populations freshly purified from prostate tissues of three prostate cancer patients by deep RNA-seq.
2015-04-30 | E-GEOD-67070 | biostudies-arrayexpress
Project description:A Basal Stem Cell Signature Identifies Aggressive Prostate Cancer Phenotypes
| PRJNA323923 | ENA
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.
2015-04-30 | GSE67070 | GEO
Project description:We propose that genes that control adult stem cell homeostasis in slowly turning over organs, such as prostate, control cancer fate. One such gene, KLF4, highly expressed in murine prostate stem cells, regulates their homeostasis, blocks malignant transformation and controls the self-renewal of tumor initiating cells. KLF4 loss induces molecular features of aggressive cancer and converts PIN lesions to invasive sarcomatoid carcinomas; its re-expression in vivo reverses this process. Bioinformatic analysis links these changes to human cancer. KLF4 and its signature containing downstream targets identify indolent tumors and predict recurrence-free survival in 2 prostate cancer cohorts. Thus, the link between normal stem cells and cancer control provides new approaches to improve prognosis and for identifying therapeutic targets for advanced cancer.
2018-12-03 | GSE114772 | GEO
Project description:Expression profiles of aggressive versus non-aggressive ovarian, breast, melanoma, and prostate cancer cell lines Expression profiles of aggressive versus non-aggressive ovarian, breast, melanoma, and prostate cancer cell lines was determined. 231MFP, C8161, SKOV3, DU145, and PC3 are aggressive and MCF7, MUM2C, OVCAR3, and LNCaP are non-aggressive cancer cells. We are not comparing across all of the cell lines--just between C8161 and MUM2C, SKOV3 and OVCAR3, 231MFP and MCF7, and LNCaP/DU145/PC3. Therefore the normalization strategies used are different. We have not used the same normalization strategy
2011-08-09 | E-GEOD-28846 | biostudies-arrayexpress
Project description:We found a novel molecular link between hyperglycaemia and the increased frequency of aggressive prostate cancer. High glucose was demonstrated to increase the expression of miR-301a which targeted Smad4 and p21, resulted in promoting the proliferation of prostate cancer cells.
2016-01-22 | GSE77092 | GEO
Project description:The role of Notch signaling in the maintenance and differentiation of adult prostate stem cells remains unclear. We found that Notch ligands are mainly expressed within the basal cell lineage, while active Notch signaling is detected in both the prostate basal and luminal cell lineages. Disrupting the canonical Notch effector RBP-J impairs the differentiation of prostate basal stem cells and increases their proliferation in vitro and in vivo, but does not affect luminal cell biology. Conversely, ectopic Notch activation in adult prostates results in basal cell depletion and luminal cell hyper-proliferation. TGFβ dominates over Notch and overrides Notch ablation-induced proliferation of prostate basal cells. In turn, Notch confers positive feedback by up-regulating a plethora of TGFβ signaling components including TGFβRI. These findings reveal crucial roles of the self-enforced positive reciprocal regulatory loop between TGFβ and Notch in maintaining prostate basal stem cell dormancy. We employed an in vitro prostate sphere assay to further investigate how Notch signaling regulates basal cell proliferation and differentiation. FACS isolated adult murine prostate basal cells (using FVB mice) were cultured in the prostate sphere assay with or without N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester (DAPT), an inhibitor for the γ-Secretase complex. Gene expression profiles were taken of vehicle- and DAPT-treated prostate spheres.
2012-11-08 | E-GEOD-34067 | biostudies-arrayexpress
Project description:We have developed a novel spontaneous model of epithelial-to-mesenchymal transition (EMT) which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-Cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressively and stem cell-like characteristics, whereas the other was non-aggressive and had no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. To understand this phenotypic differences between the clones we have conducted a microarray expression profiling experiment using Affymetrix platform.
2016-07-22 | E-MTAB-4966 | biostudies-arrayexpress