Prostate Cell News Volume 6.11 | Mar 27 2015

PLZF, a Tumor Suppressor Genetically Lost in Metastatic Castration Resistant Prostate Cancer, Is a Mediator of Resistance to Androgen Deprivation Therapy
Scientists demonstrated that knockdown of promyelocytic zinc finger protein (PLZF) expression promoted a castration-resistant prostate cancer and enzalutamide resistant phenotype in prostate cancer cells. Reintroduction of PLZF expression was sufficient to reverse androgen-independent growth mediated by PLZF depletion. [Cancer Res] Abstract

PLCε Knockdown Inhibits Prostate Cancer Cell Proliferation via Suppression of Notch Signaling and Nuclear Translocation of the Androgen Receptor
Researchers showed that phospholipase Cε (PLCε) expression was elevated in prostate cancer tissues compared to benign prostate tissues. Furthermore, PLCε depletion using an adenovirally delivered shRNA significantly decreased cell growth and colony formation, arresting the PC3 and LNCaP cell lines in the S phase of the cell cycle. [Cancer Lett] Abstract

Intensified Antineoplastic Effect by Combining an HDAC-Inhibitor, an mTOR-Inhibitor and Low Dosed Interferon Alpha in Prostate Cancer Cells
The effects of the triple application of the histone deacetylase (HDAC) inhibitor valproic acid, the mammalian target of rapamycin (mTOR) inhibitor everolimus and low dosed interferon alpha on prostate cancer cell growth and dissemination capacity were investigated. [J Cell Mol Med] Full Article

FOXA1 Modulates EAF2 Regulation of AR Transcriptional Activity, Cell Proliferation, and Migration in Prostate Cancer Cells
In human cells, the interaction of ELL-associated factor 2 (EAF2) with FOXA1 and the effect of EAF2 on the FOXA1 protein levels were determined by co-immunoprecipitation and protein stability assay. The effect of EAF2 and/or FOXA1 knockdown on the expression of AR-target genes was determined by real-time RT-PCR and luciferase reporter assays. [Prostate] Abstract

In Search of the Molecular Mechanisms Mediating the Inhibitory Effect of the GnRH Antagonist Degarelix on Human Prostate Cell Growth
The direct effect of degarelix on human prostate cell growth was evaluated. Normal prostate myofibroblast WPMY-1 and epithelial WPE1-NA22 cells, benign prostatic hyperplasia-1 cells, androgen-independent PC-3 and androgen-dependent LNCaP prostate cancer cells, as well as VCaP cells derived from a patient with castration-resistant prostate cancer were used. [PLoS One] Full Article

Combining Paclitaxel with ABT-263 Has a Synergistic Effect on Paclitaxel Resistant Prostate Cancer Cells
Scientists assessed the capability of paclitaxel, one of the taxanes, to induce death in two prostate cancer lines, LNCaP and PC3. Paclitaxel drove an apoptotic pathway in LNCaP, but not in PC3 cells, in response to G2/M arrest. [PLoS One] Full Article

Prostate Cancer Cells Stimulated by Calcium-Mediated Activation of Protein Kinase C Undergo a Refractory Period before Re-Releasing Calcium-Bearing Microvesicles
After an initial stimulus of prostate cancer cells with sublytic C5b-9 and activation of microvesicles (MV) release through PKC, cells took up to 30 minutes to fully recover their ability to microvesiculate. This release of MVs through activation of sublytic C5b-9 was inhibited by the PKC inhibitor bisindoylmaleimide I but not the Rho kinase inhibitor, Y27632. [Biochem Biophys Res Commun] Abstract

CLINICAL RESEARCH

Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer
Scientists examined circulating tumor cells alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind Phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. [J Clin Oncol] Abstract

Comparison of Clinical Outcomes between Upgraded Pathologic Gleason Score 3 + 4 and Non-Upgraded 3 + 4 Prostate Cancer Among Patients who Are Candidates for Active Surveillance
Researchers clarified differences patients with pathological Gleason score 3 + 4 according to biopsy Gleason score after radical prostatectomy among candidates for active surveillance. [World J Urol] Abstract

Implications of Ubiquitin Ligases in Castration-Resistant Prostate Cancer
The authors highlight the latest developments in the mechanisms by which E3 ubiquitin ligases control AR activity, with implications in castration-resistant prostate cancer. [Curr Opin Oncol] Abstract

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Teikoku Pharma USA Announces New Drug Application to The U.S. Food and Drug Administration for Docetaxel Injection Concentrate, Non-Alcohol Formula
Teikoku Pharma USA announced that it has submitted a 505(b)(2) New Drug Application to the U.S. Food and Drug Administration (FDA) for Docetaxel Injection Concentrate, Non-Alcohol Formula. Docetaxel Injection Concentrate, Non-Alcohol Formula is for the treatment of breast cancer, non-small cell lung cancer, prostate cancer, gastric adenocarcinoma, and head and neck cancer. [Teikoku Pharma USA, Inc.] Press Release

Sipuleucel-T in Prostate Cancer: Indication of Added Benefit
Sipuleucel-T (trade name Provenge) has been approved since September 2014 for men with metastatic prostate cancer who have few or no symptoms and do not yet require chemotherapy. In the dossier assessment conducted by the German Institute for Quality and Efficiency in Health Care in January 2015, no added benefit could be derived for sipuleucel-T. [German Institute for Quality and Efficiency in Health Care] Press Release

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NEW Postdoctoral Research Fellow – Prostate Cancer and Breast Cancer (Baylor College of Medicine)

NEW Postdoctoral Research Scientist – Prostate Cancer (Columbia University Medical Center)

NEW Postdoctoral Fellow – Development, Progression and Chemotherapy Resistance of Cancers (University of Maryland Baltimore – School of Medicine)

Postdoctoral Research Associate – Cell Signaling in Prostate Cancer (Heriot-Watt University)

Postdoctoral Fellow – Cancer Biology (Brigham & Women’s Hospital – Harvard Medical School)

Postdoctoral Position – Stem Cell Biology/Cancer Biology (Oregon Health and Science University)

Postdoctoral Research – Scientist Metabolic Adaptation in Treatment Resistant Prostate Cancer (Cancer Research UK Beatson Institute in Glasgow)

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