Prostate Cell News Volume 4.20 | May 31 2013

LABORATORY RESEARCH

O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer
The authors showed that the hexosamine biosynthetic pathway (HBP) genes are overexpressed in clinical prostate cancer and androgen-regulated in cell-lines. HBP senses metabolic status of the cell and produces an essential substrate for O-GlcNAc transferase, which regulates target proteins via glycosylation. [Cancer Res] Abstract

Peptidomimetic Targeting of Critical Androgen Receptor-Coregulator Interactions in Prostate Cancer
Scientists report the disruption of specific protein-protein interactions involving LXXLL motifs in androgen receptor-coregulator proteins such as PELP1 using a novel, small molecule peptidomimetic (D2). D2 is stable, non-toxic and efficiently taken up by prostate cancer cells. [Nat Commun] Abstract | Press Release

Identification of Novel TMPRSS2:ERG Mechanisms in Prostate Cancer Metastasis: Involvement of Metalloproteinase 9 and Plexin A2
In this study on TMPRSS2:ERG regulation in prostate cancer (PCa), researchers used an androgen receptor and TMPRSS2:ERG fusion double-negative PCa cell model: PC3c. In three cell clones with different TMPRSS2:ERG expression levels, ectopic expression of the fusion resulted in significant induction of cell migration and invasion in a dose-dependent manner. [Oncogene] Abstract

Telomere Length Influences Cancer Cell Differentiation In Vivo
Investigators showed that forced telomere elongation in cancer cells promotes their differentiation in vivo. They elongated the telomeres of human prostate cancer cells that possess short telomeres by enhancing their telomerase activity. [Mol Cell Biol] Abstract

Stromal Insulin-Like Growth Factor Binding Protein 3 (IGFBP3) Is Elevated in the Diseased Human Prostate and Promotes Ex Vivo Fibroblast-to-Myofibroblast Differentiation
Using isoform-specific lentiviral-mediated knockdown, scientists demonstrated that IGFBP3 is essential for transforming growth factor beta 1 (TGFβ1)-mediated differentiation. Whilst recombinant human IGFBP3 alone was not sufficient to induce differentiation, IGFBP3 synergistically potentiated TGFβ1-mediated stromal remodeling predominantly via an insulin-like growth factor-independent mechanism. [Endocrinology] Abstract

Ring-Substituted Analogs of 3,3′-Diindolylmethane (DIM) Induce Apoptosis and Necrosis in Androgen-Dependent and -Independent Prostate Cancer Cells
Researchers aimed to confirm the ability of 4,4′- and 7,7′-dibromo- and dichloro-substituted ring-DIMs to inhibit androgen-stimulated proliferation of androgen-dependent LNCaP human prostate cancer cells using a non-invasive, real-time monitoring technique. [Invest New Drug] Abstract

Herbal Infusions: Their Phenolic Profile, Antioxidant and Anti-Inflammatory Effects in HT29 and PC3 Cells
Scientists analyzed the phenolic profile of six herbal infusions namely Cretan marjoram, pink savory, oregano, mountain tea, pennyroyal and chamomile by LCDAD-MS and by GC-MS. Infusions exhibited the potential to inhibit cell proliferation and to reduce IL-8 levels in HT29 colon and PC3 prostate cancer cells. [Food Chem Toxicol] Abstract

Induction of Retinol-Binding Protein 4 and Placenta-Specific 8 Expression in Human Prostate Cancer Cells Remaining in Bone following Osteolytic Tumor Growth Inhibition by Osteoprotegerin
Scientists aimed to identify additional therapeutic targets that can be combined with osteoprotegerin (OPG)/receptor activator of NF-κB ligand/RANK pathway inhibition in the treatment of prostate cancer bone metastasis. They established a stable transfectant that produces high levels of OPG mRNA and protein from PC-3 human prostate cancer cells. [Int J Oncol] Abstract | Full Article

CLINICAL RESEARCH

Expression of MMP-1, MMP-9 and TIMP-2 in Prostate Carcinoma and Their Influence on Prognosis and Survival
The authors investigated the influence of matrix metalloproteinase (MMP)-1, MMP-9 and tissue inhibitors of metalloproteinase (TIMP)-2 on different clinicopathologic variables and disease-free survival of patients with prostate carcinoma. MMP-1 expression in tumor cells was associated with lower Gleason scores, pretreatment prostate-specific antigen levels and lower incidence of vascular, perineural and extracapsular invasions. [J Cancer Res Clin Oncol] Abstract

Analysis of the Correlation between Endorectal MRI Response to Neoadjuvant Chemotherapy and Biochemical Recurrence in Patients with High-Risk Localized Prostate Cancer
Data were pooled from two trials exploring neoadjuvant chemotherapy in high-risk localized prostate cancer. There were 53 evaluable patients in the combined analysis: 20 achieved a PSA response, 16 achieved an endorectal magnetic resonance imaging (erMRI) partial response and 24 achieved an erMRI minor response. [Prostate Cancer Prostatic Dis] Abstract

Hypoxia, Notch Signaling, and Prostate Cancer
The notch signaling pathway is known to regulate vascular cell fate and is responsive to hypoxia-inducible factors. Evidence to date suggests similar, therapeutically exploitable, behavior of notch-activated and hypoxic prostate cancer cells. [Nat Rev Urol] Abstract

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Health Canada Expands Indication for ZYTIGA^® in Men with Metastatic Prostate Cancer
Janssen Inc. announced that Health Canada has approved the once-daily, oral medication ZYTIGA^® (abiraterone acetate), for use in combination with prednisone for the treatment of metastatic castration-resistant prostate cancer in patients who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy. [Janssen Inc.] Press Release

New Alliance for European Excellence and Competitiveness in Life Sciences
At the Centre for Genomic Regulation, in Barcelona, directors and staff from ten top European research institutes will kick off a new alliance, called EU-LIFE, that will promote European research. The mission of EU-LIFE is to foster excellence, share knowledge, and influence policies in life sciences. [VIB] Press Release

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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)

NEW Stem Cell Biology
September 24-28, 2013
Cold Spring Harbor, United States

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NEW Postdoctoral Position – Mechanisms that Govern Prostate Cancer Progression (University of Copenhagen)

Postdoctoral Position – Castrate Resistant Prostate Cancer (Mount Sinai School)

PCUK Funded PhD Studentship – Prostate Cancer (Barts Cancer Institute, Queen Mary University of London)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

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

Researcher – Prostate Cancer (Prostate Cancer UK)

Postdoctoral Position – Metabolic and Molecular Mechanisms of Advanced Prostate Cancer (Cleveland Clinic)

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