Volume 4.13 | Apr 12

Prostate Cell News 4.13 April 12, 2013
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
Newly Identified Tumor Suppressor Provides Therapeutic Target for Prostate Cancer
Scientists have identified how an enzyme called PKCζ suppresses prostate tumor formation. The finding, which also describes a molecular chain of events that controls cell growth and metastasis, could lead to novel ways to control disease progression. [Press release from Sanford-Burnham Research Institute discussing online pre-publication in Proceedings of the National Academy of Sciences]
Press Release | Abstract

Learn More: Column-Free Enrichment of Mouse Mammary Stem & Progenitor Cells
PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

Elevation of Receptor Tyrosine Kinases by Small Molecule AKT Inhibitors in Prostate Cancer Is Mediated by Pim-1
Scientists showed that RNAi-mediated silencing or pharmacological inhibition of Pim-1 activity curtails AKT inhibitor-induced upregulation of receptor tyrosine kinases in prostate cancer cells. [Cancer Res] Abstract

Androgen-Responsive Serum Response Factor (SRF) Target Genes Regulate Prostate Cancer Cell Migration
The authors report that the contribution of two representative Serum Response Factor (SRF) effector genes that are underexpressed, calponin 2 (CNN2), or overexpressed, sidekick-homolog 1 (SDK1), in clinical prostate cancer (CaP) specimens were studied. siRNA-mediated deregulation of CNN2 or SDK1 expression did not affect CaP cell proliferation or apoptosis, but had marked effects on CaP cell morphology and actin cytoskeleton organization. [Carcinogenesis] Abstract

Indole-3-Carbinol and 3′, 3′-Diindolylmethane Modulate Androgen’s Effect on C-C Chemokine Ligand 2 and Monocyte Attraction to Prostate Cancer Cells
Researchers hypothesized that androgen could modulate C-C chemokine ligand 2 (CCL2) expression in hormone-responsive prostate cancer cells and thereby promote recruitment of monocytes. Dihydrotestosterone was found to induce a time and concentration-dependent increase in CCL2 mRNA levels in androgen-responsive human prostate cancer cells. [Cancer Prev Res] Abstract

Oncomir miR-125b Suppresses p14ARF to Modulate p53-Dependent and p53-Independent Apoptosis in Prostate Cancer
Scientists’ previous studies demonstrated that in human prostate cancer the miRNA miR-125b is highly expressed, leading to a negative regulation of some tumor suppressor genes. In this study, they further extend their studies by showing that miR-125b represses the protein product of the ink4a/ARF locus, p14ARF, in two prostate cancer cell lines, LNCaP and 22Rv1, as well as in the PC-346C prostate cancer xenograft model that lentivirally overexpressed miR-125b. [PLoS One] Full Article

PMS1077 Sensitizes TNF-α Induced Apoptosis in Human Prostate Cancer Cells by Blocking NF-κB Signaling Pathway
Investigators found that PMS1077 inhibited tumor necrosis factor-α (TNF-α) induced expression of the nuclear transcription factor-kappa B (NF-κB) regulated reporter gene in a dose dependent manner. Western blot assay indicated that PMS1077 suppressed the TNF-α induced inhibitor of κB-α (IκB-α) phosphorylation, IκB-α degradation, and p65 phosphorylation. [PLoS One] Full Article

Suppression of Interactions between Prostate Tumor Cell Integrin αvβ3 and Endothelial ICAM-1 by Simvastatin Inhibits Prostate Cancer Micrometastasis
Researchers demonstrated the potential benefits of simvastatin in the inhibition of prostate cancer micrometastasis and revealed the novel molecular mechanisms underlying this process. They showed that simvastatin inhibited the ability of human PC3 prostate cancer cells for transendothelial migration in vitro. [J Cell Physiol] Abstract

NVP-LDE-225 (Erismodegib) Inhibits Epithelial-Mesenchymal Transition and Human Prostate Cancer Stem Cell Growth in NOD/SCID IL2Rγ Null Mice by Regulating Bmi-1 and MicroRNA-128
The effects of NVP-LDE-225 on cancer stem cell’s viability, sphere formation, apoptosis, epithelial-mesenchymal transition and tumor growth in NOD/SCID IL2Rγ null mice were examined. NVP-LDE-225 inhibited cell viability and spheroid formation, and induced apoptosis by activation of caspase-3 and cleavage of poly-ADP ribose polymerase. [Oncogenesis] Full Article

CLINICAL RESEARCH

Germline BRCA Mutations Are Associated with Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer
Scientists analyzed the tumor features and outcomes of 2,019 patients with prostate cancer (PCa) (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8, T3/T4 stage, nodal involvement, and metastases at diagnosis than PCa in noncarriers. [J Clin Oncol]
Abstract | Press Release

miR-205 Negatively Regulates the Androgen Receptor and Is Associated with Adverse Outcome of Prostate Cancer Patients
Researchers demonstrated binding of microRNA-205 (miR-205) to the 3′UTR of androgen receptor (AR) and decrease of both AR transcript and protein levels. This finding was corroborated in the patient cohort were miR-205 expression inversely correlated to AR immunostaining in malignant prostate cells and to serum levels of prostate-specific antigen, an androgen-regulated protein. [Brit J Cancer] Abstract

Statin Use and Risk of Prostate Cancer and High-Grade Prostate Cancer: Results from the REDUCE Study
Statins are associated with lower PSA levels. As PSA is the primary method for prostate cancer (PC) screening, this confounds any associations between statins and risk of being diagnosed with PC. Thus, researchers examined the association between statins and cancer and high-grade cancer in REDUCE, where biopsies were largely PSA-independent. Statin use was not associated with overall PC diagnosis. [Prostate Cancer P D] Abstract

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REVIEWS
Prostate Cancer Risk-Associated Genetic Markers and Their Potential Clinical Utility
The authors first briefly review results from studies of familial aggregation and genetic susceptibility to prostate cancer (PCa). They then recap key findings of rare and high-penetrance PCa susceptibility genes from linkage studies in PCa families. They devote a significant portion of this article to summarizing discoveries of common and low-penetrance PCa risk-associated single-nucleotide polymorphisms from genetic association studies in PCa cases and controls, especially those from genome-wide association studies. [Asian J Androl] Abstract

Visit our reviews page to see a complete list of reviews in the prostate cell research field.
SCIENCE NEWS
Preclinical Data Presented at AACR Describe a Mechanism of Action of Cabozantinib in a Prostate Cancer Bone Metastasis Model
Exelixis, Inc. announced the presentation of preclinical data that provide insight into the mechanism of action of its lead compound, cabozantinib, with respect to its activity against prostate cancer tumors that have metastasized to the bone. [Press release from Exelixis, Inc. discussing research presented at The American Association for Cancer Research Annual Meeting 2013, Washington] Press Release

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INDUSTRY NEWS

As Medical Research Faces Potential Cuts, Prostate Cancer Foundation Funds 21 Young Investigators
The Prostate Cancer Foundation (PCF) announced 21 new Young Investigator awards to support the most innovative minds in the field of prostate cancer research and expand its global knowledge exchange. Including 23 Young Investigators announced in 2012, the total of PCF Young Investigators funded since 2007 now stands at 118. [Prostate Cancer Foundation] Press Release

Men, What’s Your Prostate IQ? TransMedia Creates Test To Find Out
How much do men know about their prostate?  What’s their Prostate IQ? TransMedia Group has devised a way to find out through the National Prostate IQ Test. TransMedia said it constructed the test to go along with a mobile app created by Dr. Herb Ross. The app, called Prostate Aerobics serves as a personal trainer reminding and instructing users to exercise their pelvic floor muscles to strengthen and restore prostate health. [PR Newswire Association LLC] Press Release

POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

NEW The Jackson Laboratory: Modeling Human Malignancy with Patient-Derived Xenograft Cancer Models
April 18, 1:00PM (ET in US)
Webinar

NEW Keystone Symposium: The Hippo Tumor Suppressor Network: From Organ Size Control to Stem Cells and Cancer
May 19-23, 2013
Monterey, United States

Visit our
events page to see a complete list of events in the prostate cell community.

JOB OPPORTUNITIES

PhD Studentship – Investigation into Chemokine Receptor Induced Cell Migration (University of East Anglia)

Principal Investigator – Ca2+ Channels on Tumor Angiogenesis (Lille 1 University)

Postdoctoral Research Associate – Prostate Cancer Research (University of Illinois at Chicago)

PhD Studentship – The Role of STEAP2 in Prostate Cancer Invasion and Metastasis (Swansea University)

Researcher – Prostate Cancer (Prostate Cancer UK)

Postdoctoral Position – Tumor-Propagating Cells in Prostate Cancer (University of Georgia)


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