Prostate Cell News Volume 4.24 | Jun 28 2013

Molecular Circuit Involving KLK4 Integrates Androgen and mTOR Signaling in Prostate Cancer
Researchers showed that proteins encoded by two androgen-regulated genes, kallikrein related peptidase 4 (KLK4) and promyelocytic leukemia zinc finger, integrate optimal functioning of androgen receptor and mammalian target of rapamycin (mTOR) signaling in prostate cancer (PCa) cells. KLK4 knockdown results in a significant decline in PCa cell proliferation in vitro and in vivo, decreases anchorage-independent growth, induces apoptosis, and dramatically sensitizes PCa cells to apoptosis-inducing agents. [Proc Natl Acad Sci USA] Abstract

Regulation of the Transcriptional Coactivator FHL2 Licenses Activation of the Androgen Receptor in Castrate-Resistant Prostate Cancer
Scientists identified FHL2 as a novel coactivator of ligand-independent androgen-receptor (AR) variants that are important in castrate-resistant prostate cancer. They demonstrated that the nuclear localization of FHL2 and coactivation of the AR is driven by calpain-cleavage of the cytoskeletal protein filamin, a pathway which shows differential activation in prostate epithelial versus prostate cancer cell lines. [Cancer Res] Abstract

Infiltrating Bone Marrow Mesenchymal Stem Cells Increase Prostate Cancer Stem Cell Population and Metastatic Ability via Secreting Cytokines to Suppress Androgen Receptor Signaling
Scientists showed that prostate cancer (PCa) cells could recruit bone marrow mesenchymal stem cells and consequently the metastatic ability of PCa cells was increased. They also found that the increased metastatic ability of PCa cells could be due to the increased PCa stem cell population. [Oncogene] Abstract

Id4 Deficiency Attenuates Prostate Development and Promotes PIN-Like Lesions by Regulating Androgen Receptor Activity and Expression of NKX3.1 and PTEN
Scientists investigated the effect of loss of inhibitor of differentiation 4 (Id4-/-) on adult prostate morphology. Id4-/- mice had smaller prostates with fewer tubules, smaller tubule diameters and subtle mPIN like lesions. Prostate cancer cell line models in which Id4 was either silenced or over-expressed confirmed that Id4 regulates NKX3.1, Sox9 and PTEN. [Mol Cancer] Abstract | Full Article

Lin28 Promotes Growth of Prostate Cancer Cells and Activates the Androgen Receptor
Having previously demonstrated the importance of the Lin28/let-7/Myc axis in prostate cancer (CaP), researchers tested the hypothesis that Lin28 is overexpressed in CaP and that it activates androgen receptor and promotes growth of CaP cells. They found that Lin28 is overexpressed in clinical CaP compared to benign prostates. [Am J Pathol] Abstract

Metallothionein 3: An Androgen-Upregulated Gene Enhances Cell Invasion and Tumorigenesis of Prostate Carcinoma Cells
Researchers determined the effects of androgen, cadmium, and arsenic on metallothionein (MT)1/2 and MT3 in prostate carcinoma cells, and evaluated the functional effects of MT3 on cell proliferation, invasion, and tumorigenesis. Androgen, cadmium, and arsenic treatments enhanced gene expression of MT1/2 and MT3 in prostate carcinoma LNCaP cells. [Prostate] Abstract

TLR7 Expression Is Decreased During Tumor Progression in Transgenic Adenocarcinoma of Mouse Prostate Mice and Its Activation Inhibits Growth of Prostate Cancer Cells
The authors examined the expression of toll-like receptor (TLR)7 during tumor progression of transgenic mouse model for prostate cancer mice and its role on cell growth. Strong expression of TLR7 was detected in the normal prostate epithelia of wild-type mice, but not in TLR7-deficient mice. In contrast, TLR7 expression was weak in transgenic adenocarcinoma of mouse prostate-C2 cells, as compared with murine bone marrow-derived macrophages. [Am J Reprod Immunol] Abstract

Androgen Receptors Expressed by Prostatic Stromal Cells Obtained from Younger versus Older Males Exhibit Opposite Roles in Prostate Cancer Progression
Using a gene knockdown technique and coculture system, investigators found that the knockdown of the androgen receptor (AR) in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males where AR expression was knocked down. [Asian J Androl] Full Article

CLINICAL RESEARCH

African American Men with Very Low-Risk Prostate Cancer Exhibit Adverse Oncologic Outcomes after Radical Prostatectomy: Should Active Surveillance Still Be an Option for Them?
To explore whether race-based health disparities exist among men with very low-risk prostate cancer (PCa), the authors evaluated oncologic outcomes of African American (AA) men with very low-risk PCa who were candidates for active surveillance but elected to undergo radical prostatectomy (RP). AA men with very low-risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. [J Clin Oncol] Abstract

Role of Engrailed-2 (EN2) as a Prostate Cancer Detection Biomarker in Genetically High Risk Men
Controversy surrounds the use of PSA as a biomarker for prostate cancer detection, leaving an unmet need for a novel biomarker in this setting; urinary EN2 may identify individuals with clinically relevant prostate cancer. Urine samples from 413 BRCA1 and BRCA2 mutation carriers and controls were evaluated. There was no statistically significant difference in EN2 levels according to genetic status or Gleason score. [Sci Rep] Full Article

Overview of the Latest Treatments for Castration-Resistant Prostate Cancer
Over the past few years, researchers have developed an increased understanding of the molecular mechanisms that underlie prostate cancer progression and castration resistance and expanded their repertoire of therapeutic options for castration-resistant prostate cancer (CRPC). Four new agents have been shown to prolong overall survival in patients with CRPC in the postchemotherapy setting. [Nat Rev Urol] Abstract

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XTANDI™ Authorized in the European Union for Advanced Prostate Cancer
Astellas Pharma Europe Ltd. and Medivation, Inc. announced that following the regulatory review process by the European Medicines Agency and a positive Committee for Medicinal Products for Human Use opinion the European Commission has granted the marketing authorization for XTANDI capsules for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy. [Astellas Pharma Europe Ltd.] Press Release

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Postdoctoral Position – Cancer Biology and Chemotherapy Resistance (Dalhousie University)

Postdoctoral Fellow – Drug Discovery/GU Oncology (Moffitt Cancer Center & Research Institute)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

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)

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