Prostate Cell News Volume 10.23 | Jun 28 2019

TOP STORY

Arginine Vasopressin Receptor 1a Is a Therapeutic Target for Castration-Resistant Prostate Cancer

Depletion of arginine vasopressin receptor 1a (AVPR1A) in castration-resistant prostate cancer (PC) cells resulted in decreased cell proliferation and reduced cyclin A. In contrast, androgen-dependent PC, androgen receptor-negative PC, or nontumorigenic prostate epithelial cells, which had undetectable AVPR1A mRNA, were minimally affected by AVPR1A depletion. [Sci Transl Med] Full Article

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Olfactomedin 4 Downregulation Is Associated with Tumor Initiation, Growth, and Progression in Human Prostate Cancer

Three of the eight CpG sites in the olfactomedin 4 (OLFM4) gene promoter region were hypermethylated in cancerous prostate cells compared with adjacent normal cells, and reduced methylation of eight CpG sites was associated with increased OLFM4 mRNA expression in RWPE1 and PC3 cells. Furthermore, knockdown of OLFM4 gene expression was associated with enhanced epithelial-mesenchymal transition-marker expression in RWPE immortalized normal prostate cells. [Int J Cancer] Abstract

KLF4 as a Rheostat of Osteolysis and Osteogenesis in Prostate Tumors in the Bone

Investigators showed that the anti-tumorigenic effect of KLF4 extended to PC3 human prostate cancer cells growing in the bone. They compared KLF4 null cells with cells transduced with a DOX-inducible KLF4 expression system, and found KLF4 function inhibited PC3 growth in monolayer and soft agar cultures. [Oncogene] Abstract

Parallel-Reaction Monitoring-Based Proteome-Wide Profiling of Differential Kinase Protein Expression During Prostate Cancer Metastasis In Vitro

The authors applied their recently reported parallel-reaction monitoring-based targeted proteomic method to examine the reprogramming of the human kinome associated with bone metastasis of prostate cancer in vitro. The method displayed superior sensitivity over the shotgun-proteomic approach, and it facilitated the quantification of the relative expression of 276 kinase proteins in a pair of bone metastatic prostate cancer cells. [Anal Chem] Abstract

The SOX4/miR-17-92/RB1 Axis Promotes Prostate Cancer Progression

Researchers showed that sex-determining region Y-box 4 (SOX4) expression was associated with prostate cancer progression and the development of the neuroendocrine phenotype in androgen deprivation conditions. High-throughput microRNA profiling and bioinformatics analyses suggested that SOX4 may target the miR-17-92 cluster. [Neoplasia] Full Article

Mesenchymal Stem Cell-Mediated Delivery of Therapeutic Adenoviral Vectors to Prostate Cancer

Scientists generated mesenchymal stem cell-derived packaging cells for adenoviruses by modifying human mesenchymal stem cells with the adenovirus E1A/B genes needed for viral replication. Using cell-based assays, they demonstrated that two adenoviral vectors, replication-defective adenovirus expressing p14 and p53 or conditionally replicating oncolytic adenovirus, packaged by E1A/B-modified mesenchymal stem cells, suppressed the growth of prostate cancer cells in culture. [Stem Cell Res Ther] Full Article

Loss of KMT2D Induces Prostate Cancer ROS-Mediated DNA Damage by Suppressing the Enhancer Activity and DNA Binding of Antioxidant Transcription Factor FOXO3

The function of KMT2D regarding DNA damage in prostate cancer and the underlying mechanisms of KMT2D in epigenetic regulation were explored in a series of studies. Knockdown of KMT2D sensitized cells to DNA damage through the disturbance of antioxidative gene expression and increased levels of intracellular reactive oxygen species (ROS), which led to cell apoptosis and senescence. [Epigenetics] Abstract

E-Cadherin Is Downregulated in Benign Prostatic Hyperplasia and Required for Tight Junction Formation and Permeability Barrier in the Prostatic Epithelial Cell Monolayer

The ultra-structure of cellular junctions in benign prostatic hyperplasia (BPH) specimens was observed using transmission electron microscopy and E-cadherin immunostaining analysis was performed on BPH and normal adjacent specimens from BPH patients. In vitro cell line studies using benign prostatic epithelial cell lines were performed to determine the impact of small interfering RNA knockdown of E-cadherin on transepithelial electrical resistance and diffusion of fluorescein isothiocyanate-dextran in transwell assays. [Prostate] Abstract

miR-221-5p Regulates Proliferation and Migration in Human Prostate Cancer Cells and Reduces Tumor Growth In Vivo

The functional role of miR-221-5p was characterized in androgen- dependent and androgen- independent prostate cancer cell line models by miR-221-5p overexpression and knock-down experiments. The metastatic potential of highly aggressive PC-3M-Pro4 cells over-expressing miR-221-5p was determined by studying extravasation in a zebrafish model. [BMC Cancer] Full Article

Identifying Small Molecule Probes of ENTPD5 through High Throughput Screening

Investigators performed a high-throughput screen of 21,120 compounds to identify small molecule inhibitors of ectonucleoside triphosphate diphosphohydrolase 5 (ENPTD5) activity. Two hits were identified, and they performed a structure activity relationship screen around these hits. [PLoS One] Full Article

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Tumor-Proximal Liquid Biopsy to Improve Diagnostic and Prognostic Performances of Circulating Tumor Cells

Circulating tumor cell detection and numeration are becoming part of the common clinical practice, especially for breast, colon and prostate cancer. However, their paucity in peripheral blood samples is an obstacle for their identification. [Mol Oncol] Abstract | Full Article

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Data Presented Highlights Potential of Progenics’ PSMA-Targeted Imaging Agent, PyL, in Detecting Prostate Cancer

Progenics Pharmaceuticals, Inc. announced that results from studies highlighting the PSMA-targeted imaging agent, PyL, were presented, including data from the company’s Phase II/III OSPREY trial in men with high risk and metastatic prostate cancer and three presentations from an investigator-sponsored study conducted under the company’s PyL Research Access Program™ that evaluated PyL in men with biochemically recurrent prostate cancer. [Press release from Progenics Pharmaceuticals, Inc. discussing research presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2019 Annual Meeting] Press Release

NORD Awards Ten New Grants in Eight Disease States for Rare Disease Research

The National Organization for Rare Disorders^® (NORD) has announced ten new grants as part of its Rare Disease Research Grant Program, which celebrates its 30^th anniversary in 2019. [The National Organization for Rare Disorders] Press Release

MU Receives $8.6 Million Federal Grant for New Biomedical Research Center

The University of Missouri (MU) announced that researchers in the College of Agriculture, Food and Natural Resources have received an $8.6 million grant from the National Institutes of Health to establish a new national research center. The Swine Somatic Cell Genome Editing Center will focus on aiding the development of biomedical treatments for human diseases such as cystic fibrosis. [The University of Missouri] Press Release

More Scientists Dismissed for Undisclosed Foreign Ties, Says NIH

The US National Institutes of Health (NIH) says that universities have fired scientists and refunded grant money as a result of the agency’s efforts to enforce a requirement that grantees report foreign ties, reports Science. The agency says these actions have occurred more than has been publicly reported so far. [The Scientist] Editorial

Discrimination Drives LGBT+ Scientists to Think About Quitting

Nearly one-third of physical scientists from sexual and gender minorities in the United Kingdom have considered leaving their jobs because of their workplace climate, suggests a survey. And 18% who are lesbian, gay, bisexual, transgender or from other sexual and gender minorities (LGBT+) said they had experienced harassment, bullying or exclusionary behavior in the workplace. [Nature News] Editorial

Proposal to Close UK Mouse-Research Center Is ‘Major Threat’

Leaders and senior scientists at a national mouse-genetics center in the United Kingdom have written an open letter decrying a recommendation to close the facility’s on-site academic research unit. The closure of the MRC Harwell Institute’s Mammalian Genetics Unit – where scientists study disease using animal models – would be “a major threat to mouse genetics in the UK”, says the letter, organized by 14 senior Harwell scientists. [Nature News] Editorial

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September 9-12, 2019
Boston, Massachusetts, United States

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NEW Postdoctoral Position – Prostate Biology (University of Washington)

Postdoctoral Scientist – Prostate Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Researcher – Prostate and Breast Cancer Progression (The Garvan Institute)

Postdoctoral Fellow – Jak-Stat Signaling in Prostate and Pancreatic Cancer (Medical College of Wisconsin)

Research Scientist – Cancer Cell Line Development (QLB Biotherapeutics, Inc.)

Postdoctoral Researcher – Neutrophils in Prostate and Pancreatic Cancer (University of Nebraska Medical Center)

Postdoctoral Fellow – Nanomedicine in Prostate Cancer (Queen’s University Belfast)

Postdoctoral Position – Cancer Cell Biology (University of Zurich)

Postdoctoral Position – Prostate Cancer (UT Health San Antonio)

Postdoctoral Position – Microenvironment & Cancer (Brigham and Women’s Hospital)

Postdoctoral Fellow – Prostate Cancer & Stem Cell Biology (City of Hope)

Postdoctoral Fellow – Cancer Immunotherapy (University of Notre Dame)

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