Prostate Cell News Volume 5.02 | Jan 24 2014

Rapid Induction of Androgen Receptor Splice Variants by Androgen Deprivation in Prostate Cancer
Prostate cancer (PCa) xenografts were examined to identify mechanism of progression after castration and abiraterone. Androgen receptor (AR) reactivation in abiraterone-resistant VCaP xenografts was not associated with restoration of intratumoral androgens or alterations in AR co-regulators. [Clin Cancer Res] Abstract

The Role of sLZIP in Cyclin D3-Mediated Negative Regulation of Androgen Receptor Transactivation and Its Involvement in Prostate Cancer
Researchers investigated the distinct roles of small leucine zipper protein (sLZIP) in proliferation of androgen-dependent and -independent prostate cancer (PCa) cells. Cyclin D3 is known to interact with androgen receptor (AR) and attenuates the ligand-dependent function of AR in PCa cells. [Oncogene] Abstract

Regulation of the Proapoptotic Functions of Prostate Apoptosis Response-4 (Par-4) by Casein Kinase 2 in Prostate Cancer Cells
Scientists demonstrated both in rat and humans that Par-4 is a new substrate of the survival kinase casein kinase 2 (CK2) and phosphorylation by CK2 impairs Par-4 proapoptotic functions. They also unravelled different levels of CK2-dependent regulation of Par-4 between species. [Cell Death Dis] Full Article

Metastasis of Prostate Cancer and Melanoma Cells in a Preclinical In Vivo Mouse Model Is Enhanced by L-Plastin Expression and Phosphorylation
Researchers investigated the relevance of L-plastin expression and phosphorylation by ectopical expression of L-plastin in human melanoma cells and knock-down of endogenous L-plastin in prostate cancer. Knock-down of endogenous L-plastin in human prostate carcinoma cells led to reduced tumor cell growth and metastasis. [Mol Cancer] Full Article

Metformin Inhibits Androgen-Induced IGF-IR Upregulation in Prostate Cancer Cells by Disrupting Membrane Initiated Androgen Signaling
Scientists evaluated whether Metformin may affect androgen-dependent IGF-IR upregulation. In androgen receptor positive LNCaP prostate cancer cells, they found that Metformin inhibits androgen-induced CRE activity and IGF-IR gene transcription. [Endocrinology] Abstract

DNA Damage Response (DDR) via NKX3.1 Expression in Prostate Cells
Researchers demonstrated that the DNA damage induced by CPT-11, doxorubicin, and H₂O₂, but not by etoposide, is negatively influenced by NKX3.1 expression. [J Steroid Biochem Mol Biol] Abstract

ERG-SOX4 Interaction Promotes Epithelial-Mesenchymal Transition in Prostate Cancer Cells
ERG regulated SOX4 expression via binding to its promoter. Silencing both of them showed duplicate effects on restoring the epithelial characteristics, increasing cellular adhesion and decreasing capacity of cellular migration and invasion. [Prostate] Abstract

TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth In Vivo
Scientists provide evidence that tumor suppressor candidate 3 (TUSC3) is part of the oligosaccharyltransferase complex and affects N-linked glycosylation in mammalian cells. Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. [Sci Rep] Full Article

CLINICAL RESEARCH

Genetic Variations in TP53 Binding Sites Are Predictors of Clinical Outcomes in Prostate Cancer Patients
Since the tumor protein p53 (TP53), a transcription factor, plays a crucial role in prostate cancer development and progression, we hypothesized that sequence variants in TP53 binding sites might affect clinical outcomes in patients with prostate cancer. We systematically evaluated 41 single nucleotide polymorphisms within genome-wide predicted TP53 binding sites in a cohort of 1,024 prostate cancer patients. [Arch Toxicol] Full Article

Enzalutamide after Docetaxel and Abiraterone Therapy in Metastatic Castration-Resistant Prostate Cancer
Thirty-five metastatic castration-resistant prostate cancer patients in the German compassionate use program, who received enzalutamide after progression with taxane-based chemotherapy and abiraterone were prospectively evaluated. [Adv Ther] Abstract

Emerging Roles of Radioresistance in Prostate Cancer Metastasis and Radiation Therapy
The authors discuss the novel findings of phosphoinositide 3-kinase/Akt/phosphatase and tensin homolog/mammalian target of rapamycin signaling pathway, autophagy, epithelial-mesenchymal transition and cancer stem cells in the regulation of prostate cancer (CaP) metastasis and radioresistance, and focus on combination of radiosensitizers with radiation therapy in the treatment of CaP in preclinical studies to explore novel approaches for future clinical trials. [Cancer Metastasis Rev] Full Article

Metastatic Castration-Resistant Prostate Cancer (CRPC): Preclinical and Clinical Evidence for the Sequential Use of Novel Therapeutics
The authors summarize the preclinical and clinical data available with regards to sequencing of the novel treatments for CRPC. [Cancer Metastasis Rev] Full Article

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The HUB Foundation for Organoid Technology and STEMCELL Technologies Sign Agreement on the Manufacturing of Cell Culture Media for Organoids
The HUB Foundation for Organoid Technology announced that it has signed a licensing agreement with STEMCELL Technologies Inc. for the manufacturing and worldwide distribution of cell culture media for growing Organoids. Organoids are mini-organs grown in tissue culture from small pieces of tissue derived from patients with cancer and other diseases, and represent an exciting new tool for scientific research and drug discovery and validation. [STEMCELL Technologies Inc.] Press Release

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Postdoctoral Fellow – Molecular Mechanisms of Cancer Progression (University of South Alabama)

Postgraduate Position – Chemokine Receptor Induced Cell Migration (University of East Anglia)

Graduate Student Position – Epigenetics and Chromatin (University of Victoria)

Postdoctoral Fellow – Mechanism of Prostate Cancer Bone Metastasis (Georgia Regents University)

Postdoctoral Position – Prostate Cancer Research (Weill Cornell Medical College)

Postdoctoral Position – Stem Cells and Bioengineering (Queensland University of Technology/Translational Research Institute)

Postdoctoral Fellow – Molecular Mechanisms of Prostate Cancer (Northwestern University – Feinberg School of Medicine)

Clinical MD – Clinical Development Program for Oncology and Autoimmune Diseases (Immunomedics, Inc.)

Chief Medical Officer – Novel Therapeutics in Oncology and Autoimmune Disease (Immunomedics, Inc.)

Postdoctoral Position – Chemistry and Prostate Cancer Imaging (University of California San Francisco)

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