Prostate Cell News Volume 7.37 | Oct 07 2016

TOP STORY

Bmi1 Marks Distinct Castration-Resistant Luminal Progenitor Cells Competent for Prostate Regeneration and Tumor Initiation

Investigators showed that the polycomb repressor protein Bmi1 marks a population of castration-resistant luminal epithelial cells enriched in the mouse proximal prostate. They employed lineage tracing to show that these castration-resistant Bmi1-expressing cells are capable of tissue regeneration and self-renewal. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Activation of Notch1 Synergizes with Multiple Pathways in Promoting Castration-Resistant Prostate Cancer

Scientists demonstrated that localized high-risk prostate cancer and metastatic castration-resistant prostate cancer, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. [Proc Natl Acad Sci USA] Full Article

Crosstalk between Androgen and Pro-Inflammatory Signaling Remodels Androgen Receptor and NF-κB Cistrome to Reprogram the Prostate Cancer Cell Transcriptome

To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, researchers interrogated the crosstalk between androgen receptor and NF-κB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in prostate cancer cells. [Nucleic Acids Res] Full Article

Targeting Hypoxic Prostate Tumors Using the Novel Hypoxia-Activated Prodrug OCT1002 Inhibits Expression of Genes Associated with Malignant Progression

The authors investigated the role of hypoxia in prostate tumor progression and evaluated the ability of the novel unidirectional hypoxia-activated prodrug OCT1002 to enhance the anti-tumor effect of bicalutamide. [Clin Cancer Res] Abstract

Systematic and Functional Characterization of Novel Androgen Receptor Variants Arising from Alternative Splicing in the Ligand-Binding Domain

Scientists identified a novel constitutively active androgen receptor (AR) variants (AR-V), ARv5es and established a method to predict potential activities of AR-Vs carrying impaired ligand-binding domain. [Oncogene] Full Article

Fractionated Radiation Exposure Amplifies the Radioresistant Nature of Prostate Cancer Cells

The authors showed that the RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy. [Sci Rep] Full Article

The Andean Anticancer Herbal Product BIRM Causes Destabilization of Androgen Receptor and Induces Caspase-8 Mediated-Apoptosis in Prostate Cancer

Researchers aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. [Oncotarget] Full Article

Prostate Cancer Cells in Different Androgen Receptor Status Employ Different Leucine Transporters

Scientists used LNCaP and DU145 and PC-3 cell lines as a model of androgen dependent, and metastatic prostate cancer. A new “LN-cr” cell line was established after culturing LNCaP cells for 6 months under androgen-free conditions, which is considered a model of castration resistant prostate cancer with androgen receptor expression. [Prostate] Abstract

High-Content Screening Identifies Src Family Kinases as Potential Regulators of AR-V7 Expression and Androgen-Independent Cell Growth

The authors aimed to explore existing classes of small molecules that may regulate androgen receptor (AR)-V7 expression and intracellular localization and their potential therapeutic role in castration-resistant prostate cancer. [Prostate] Abstract

Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone

The authors showed differential keratin 13 (KRT13) is enriched in benign stem-like cells that display androgen-resistance, apoptosis-resistance, and branching morphogenesis properties. Their data demonstrates that KRT13 expression is associated with poor prognosis at multiple stages of disease progression and may represent an important biomarker of adverse outcome in patients with prostate cancer. [PLoS One] Full Article

CLINICAL RESEARCH

Paired High-Content Analysis of Prostate Cancer Cells in Bone Marrow and Blood Characterizes Increased Androgen Receptor Expression in Tumor Cell Clusters

Researchers adapted our single-cell high-content liquid biopsy platform to bone marrow aspirates, to concurrently identify and characterize prostate cancer cells in patients’ blood and bone and thus discern features associated to tumorigenicity and dynamics of metastatic progression. [Clin Cancer Res] Abstract

Alternative Splicing and Cell Survival: From Tissue Homeostasis to Disease

The authors highlight some of the best-known examples of alternative splicing events involved in cell survival. Emphasis is given to the role of this regulation in human cancer and in the response to chemotherapy, providing examples of how alternative splicing of apoptotic genes can be exploited therapeutically. [Cell Death Differ] Abstract

Inflammatory Mediators in the Development and Progression of Benign Prostatic Hyperplasia

The authors discuss several stimuli, including infectious agents, urinary reflux, metabolic syndrome, the aging process, and autoimmune response, that have been described as triggers for the dysregulation of the prostatic immune system via different molecular pathways involving the development of inflammatory infiltrates. [Nat Rev Urol] Abstract

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Dr. Allen Eaves of STEMCELL Technologies Inc. Named EY Entrepreneur of the Year™ Pacific 2016

Dr. Allen Eaves, Chairman, President and Chief Executive Officer of STEMCELL Technologies, a global biotechnology company that supplies tools and services to enable life science research, is this year’s Entrepreneur Of The Year Pacific winner. [STEMCELL Technologies (Ernst & Young)] Press Release

The Nobel Assembly at Karolinska Institutet Has Decided to Award the 2016 Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi

This year’s Nobel Laureate discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components. [Nobel Media MB] Press Release | Editorial

Grant to TSRI-Led Consortium Expands to $207 Million

The National Institutes of Health, as part of its national Precision Medicine Initiative Cohort Program, has expanded a five-year funding award to The Scripps Research Institute (TSRI) from $120 million to $207 million for research to improve ability to prevent and treat disease. [The Scripps Research Institute] Press Release

Marc and Lynne Benioff’s $20 Million Gift to USC Supports Research and Treatment Innovations to Fight Cancer

USC Trustee Marc Benioff ’86 and his wife, Lynne, have given $20 million toward construction of the Lawrence J. Ellison Institute for Transformative Medicine of USC, a new center in Los Angeles that will combine interdisciplinary research with the holistic prevention and treatment of cancer. [University of Southern California] Press Release

Dramatic Twists Could Upend Patent Battle over CRISPR Genome-Editing Method

The 9-month-old patent battle over CRISPR, a novel genome-editing tool that could have immense commercial value, has taken two surprising twists. Last week, attorneys for the Broad Institute in Cambridge, Massachusetts, one of the research organizations vying for CRISPR rights, submitted motions that could let it win even if it loses. [Science Insider] Editorial

Democratic Databases: Science on GitHub

Scientists are turning to a software–development site to share data and code. [Nature Toolbox] Editorial

Brexit Government’s Anti-Immigration Stance Spooks UK Scientists

UK scientists say they’re dismayed by their new government’s toughened stance on curbing immigration, including ideas to restrict the flow of foreign students and workers. [Nature News] Editorial

UK Bioethicists Eye Designer Babies and CRISPR Cows

From designer babies to engineered mosquitoes, advances in genome-editing technologies such as CRISPR–Cas9 have raised the possibility of tremendous scientific advances — and serious ethical concerns. [Nature News] Editorial

NEW The Biology of Regenerative Medicine
April 25-27, 2017
Hinxton, United Kingdom

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NEW Postdoctoral Fellowships – Prostate Disease (Cleveland Clinic Lerner Research Institute)

Postdoctoral Position – Prostate Cancer Genomics (The Ohio State University, College of Pharmacy)

PhD Student – Molecular Pathways of Prostate Cancer Progression (German Cancer Research Centre – Helmholtz Association)

Postdoctoral Fellow – Prostate Cancer Biology (University of Maryland)

Chair of Medical Biology (Masaryk University)

Postdoctoral Fellow(s) – Uterine Fibroids and Prostate Cancer (University of Texas Health Science Center at San Antonio)

Research Intern – Prostate Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Researcher – Prostate Cancer (Oregon Health & Science University)

Professor – Prostate Cancer Research (Boston University School of Medicine)

Senior VP and Director Clinical Research – Oncology (Fred Hutchinson Cancer Research Center)

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