Prostate Cell News Volume 8.15 | Apr 28 2017

TOP STORY

Estrogen Receptor β, a Regulator of Androgen Receptor Signaling in the Mouse Ventral Prostate

As estrogen receptor β^−/− (ERβ^−/−) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, researchers used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young and aging ERβ^−/− mice and their wild type littermates. [Proc Natl Acad Sci USA] Abstract

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LABORATORY RESEARCH

Analytic, Pre-Analytic and Clinical Validation of p53 Immunohistochemistry for Detection of TP53 Missense Mutation in Prostate Cancer

TP53 missense mutations may help to identify prostate cancer (PCa) with lethal potential. The authors pre-analytically, analytically and clinically validated a robust immunohistochemistry assay to detect subclonal and focal TP53 missense mutations in PCa. [Clin Cancer Res] Abstract

Dysregulation of INF2-Mediated Mitochondrial Fission in SPOP-Mutated Prostate Cancer

Investigators revealed that speckle-type POZ protein (SPOP) recognizes a Ser/Thr-rich motif in the C-terminal region of inverted formin 2 (INF2) and triggers atypical polyubiquitination of INF2. These ubiquitination modifications did not lead to INF2 instability, but rather reduced INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogating its ability to facilitate mitochondrial fission. [PLoS Genet] Full Article

ETS Related Gene mediated Androgen Receptor Aggregation and Endoplasmic Reticulum Stress in Prostate Cancer Development

Scientists showed that ETS related gene (ERG), through its physical interaction with androgen receptor, induces androgen receptor aggregation and endoplasmic reticulum (ER) stress in the prostate glands of ERG transgenic mice. Histomorphological alterations and the expression of ER stress sensors Atf6, Ire1α, Perk, their downstream effectors Grp78/BiP and eIF2α in ERG transgenic mouse prostate glands indicate the presence of chronic ER stress. [Sci Rep] Full Article

Human Prostate Luminal Cell Differentiation Requires NOTCH3 Induction by p38-MAPK and MYC

Researchers tested the hypothesis that p38-MAPK regulation of NOTCH3, via MYC, is required for luminal differentiation. Inhibition or knockdown of p38α and/or p38δ prevented proper differentiation. Treatment with a γ-secretase inhibitor or knockdown of NOTCH1 and/or NOTCH3 greatly impaired differentiation and caused luminal cell death. [J Cell Sci] Full Article

Label Retention and Stem Cell Marker Expression in the Developing and Adult Prostate Identifies Basal and Luminal Epithelial Stem Cell Subpopulations

The authors have taken advantage of the relatively quiescent nature of stem cells to identify the slow-cycling label-retaining stem cell (LRC) populations of the prostate gland. Mice were pulsed with bromodeoxyuridine during prostate organogenesis, and the LRC populations were then identified and characterized in five-day-old and in six-month-old adult animals using immunohistochemistry and immunofluorescence. [Stem Cell Res Ther] Full Article

Comprehensive Two-Dimensional PC-3 Prostate Cancer Cell Membrane Chromatography for Screening Anti-Tumor Components from Radix Sophorae flavescentis

Scientists devised a comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatography system for screening anti-prostate cancer components in Radix S. flavescentis. Gefitinib and dexamethasone were chosen as positive and negative drugs respectively for validating and optimizing the selectivity and suitability of the comprehensive two-dimensional chromatographic system. [J Sep Sci] Abstract

Inhibition of the Insulin-Like Growth Factor-1 Receptor Potentiates Acute Effects of Castration in a Rat Model for Prostate Cancer Growth in Bone

To test if acute effects of androgen deprivation therapy was enhanced by concurrent inhibition of pro-survival insulin-like growth factor 1 (IGF-1), rats were inoculated with Dunning R3327-G tumor cells into the tibial bone marrow cavity and established tumors were treated with castration in combination with IGF-1 receptor inhibitor NVP-AEW541, or by each treatment alone. [Clin Exp Metastasis] Full Article

CLINICAL RESEARCH

Lutetium-177-Labeled Anti-Prostate-Specific Membrane Antigen Antibody and Ligands for the Treatment of Metastatic Castrate-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Investigators performed a systematic review and meta-analysis to assess the therapeutic response of lutetium-177-prostate-specific membrane antigen in the treatment of metastatic castration-resistant prostate cancer. [Prostate Cancer Prostatic Dis] Abstract

The ETS Family of Oncogenic Transcription Factors in Solid Tumors

Findings over the past decade have identified aberrant activation of the ETS transcription factor family throughout all stages of tumorigenesis. Specifically in solid tumors, gene rearrangement and amplification, feed-forward growth factor signaling loops, formation of gain-of-function co-regulatory complexes and novel cis-acting mutations in ETS target gene promoters can result in increased ETS activity. The authors discuss these different mechanisms of ETS activation and subsequent oncogenic implications, as well as the clinical utility of ETS factors. [Nat Rev Cancer] Abstract

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3D Signatures Inc. Receives First Prostate Cancer Blood Samples for Precise Clinical Trial

3D Signatures Inc. to announced that it has received the first batch of blood samples for the PRECISE prostate cancer clinical trial. The samples were received for processing and analysis at the company’s new laboratory and corporate headquarters in the MaRS Discovery District, Toronto, Canada. [3D Signatures Inc.] Press Release

OncBioMune, AqVida Partner for Commercializing Cancer and Other Generic Drugs in Mexico

OncBioMune Pharmaceuticals, Inc. announced an exclusive distribution and licensing agreement between OncBioMune and AqVida GmbH. AqVida is granting OncBioMune the rights to several oncology and other generic pharmaceuticals in their portfolio, including imatinib, docetaxel and azathioprine for commercialization in the Mexican markets. [OncBioMune Pharmaceuticals, Inc.] Press Release

$10 Million Settlement over Alleged Misconduct in Boston Heart Stem Cell Lab

A research misconduct investigation of a prominent stem cell lab by the Harvard University-affiliated Brigham and Women’s Hospital in Boston has led to a massive settlement with the U.S. government over allegations of fraudulently obtained federal grants. [ScienceInsider] Editorial

Controversial UK Research Reform Crosses Finish Line

A controversial and wide-ranging shake-up of the United Kingdom’s research and higher-education landscape has been completed, amid a huge rush by the country’s parliament to push through legislation. [Nature News] Editorial

Marine Le Pen Is a ‘Terrible Danger,’ French Research Leaders Say

The French science and higher education community appears virtually united in its opposition against Marine Le Pen, the far-right candidate who could become France’s next president during the second round of elections on 7 May. In an unprecedented letter, the directors of nine major public research institutes describe Le Pen’s candidacy as a “terrible danger” and call on voters not to support her. [ScienceInsider] Editorial

NEW Protein Aggregation in Health and Disease
June 11-16, 2017
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NEW Rapid Signaling and Genomic Steroid Hormone Actions in Health and Disease
June 11-16, 2017
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NEW Postdoctoral Fellow – Translational Prostate Cancer Research (Weill Cornell Medicine)

Postdoctoral Fellow Positions – Gene Regulation in Cancer Progression (University of Texas Health Science Center at San Antonio)

Postdoctoral Scientist – Structural Studies (Medical Research Council)

Postdoctoral Fellow – Prostate Cancer (University of South Carolina-School of Medicine)

Faculty Position – Genitourinary Oncology (Northwestern University)

Scientist – Prostate Cancer Research (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Cancer Biology (Northwestern University)

Postdoctoral Fellow – Prostate Cancer (Johns Hopkins University)

Postdoctoral Fellow – Prostate/Pancreatic Cancer (Medical College of Wisconsin)

Postdoctoral Fellow – Prostate Cancer Research (Vancouver Prostate Center)

PhD Student – Prostate Cancer Research (Vancouver Prostate Center)

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