Prostate Cell News Volume 4.12 | Apr 5 2013

LABORATORY RESEARCH

A Preclinical Xenograft Model of Prostate Cancer Using Human Tumors
Researchers developed a system for efficiently xenografting localized human prostate cancer tissue, and they adapted this protocol to study the interactions between the specific subsets of epithelial and stromal cells. Fresh prostate tissues or isolated epithelial cells were recombined with mouse seminal vesicle mesenchyme and grafted under the renal capsule of immunodeficient mice for optimum growth and survival. [Nat Protoc] Abstract

Prostate Cancer-Associated Mutations in Speckle-Type POZ protein (SPOP) Regulate Steroid Receptor Coactivator 3 Protein Turnover
In prostate cancer (PC), the p160 steroid receptor coactivators (SRCs) play critical roles in androgen receptor transcriptional activity, cell proliferation, and resistance to androgen deprivation therapy. Investigators demonstrated that the E3 ubiquitin ligase adaptor speckle-type poxvirus and zinc finger (POZ) domain protein (SPOP) interacts directly with SRC-3 and promotes its cullin 3-dependent ubiquitination and proteolysis in breast cancer, thus functioning as a potential tumor suppressor. They report that PC-associated SPOP mutants cannot interact with SRC-3 protein or promote its ubiquitination and degradation. [Proc Natl Acad Sci USA] Abstract

Androgen Receptor-Independent Function of FoxA1 in Prostate Cancer Metastasis
Through genomic analysis scientists revealed that FoxA1 regulates two distinct oncogenic processes via disparate mechanisms. FoxA1 induces cell growth requiring the androgen receptor (AR) pathway. On the other hand, FoxA1 inhibits cell motility and epithelial-to-mesenchymal transition through AR-independent mechanism directly opposing the action of AR signaling. [Cancer Res] Abstract

Monoallelic Expression of TMPRSS2/ERG in Prostate Cancer Stem Cells
Recently, it was shown that up to 80% of prostate tumors harbor at least one such gene fusion, and that the most common fusion event, between the prostate-specific TMPRSS2 gene and the ERG oncogene, is a critical, and probably early factor in prostate cancer development. Scientists demonstrated the presence and expression of this significant chromosomal rearrangement in prostate cancer stem cells. [Nat Commun] Abstract | Press Release

Elevated snoRNA Biogenesis Is Essential in Breast Cancer
Researchers report that small nucleolar RNAs (snoRNAs), and fibrillarin are frequently overexpressed in both murine and human breast cancer as well as in prostate cancers, and significantly, that this overexpression is essential for tumorigenicity in vitro and in vivo. [Oncogene] Abstract

PTPL1 and PKCδ Contribute to Proapoptotic Signaling in Prostate Cancer Cells
Scientists report a proapoptotic role for PTPL1 in PC3 and LNCaP prostate cancer cells, as its absence induces apoptosis resistance upon treatment with different drugs. In PC3 cells, PTPL1 silencing by small interfering RNA influences the expression levels of Bcl-xL and Mcl-1S proteins as well as final events in the apoptotic process such as activation of caspases and caspase-mediated cleavage of proteins like Mcl-1 or poly (ADP-ribose) polymerase. [Cell Death Dis] Full Article

Endothelial Cells Enhance Prostate Cancer Metastasis via IL6→Androgen Receptor→TGFβ→MMP9 Signals
Investigators found that CD31-positive and CD34-positive endothelial cells (ECs) are increased in prostate cancer (PCa) compared to normal tissues and these ECs cells were decreased upon castration, gradually recovered with time, and become increased after PCa progresses into the castration resistant stage, suggesting a potential linkage of these ECs with androgen deprivation therapy. [Mol Cancer Ther] Abstract

Probing the Interaction Forces of Prostate Cancer Cells with Collagen I and Bone Marrow Derived Stem Cells on the Single Cell Level
Using atomic force microscopy (AFM) based force spectroscopy, the mechanical pattern of the adhesion to SCP1 cells was characterized for two prostate cancer cell lines and compared to a substrate consisting of pure collagen type I. PC3 cells dissipated more energy during the forced de-adhesion AFM experiments and showed significantly more adhesive and stronger bonds compared to LNCaP cells. [PLoS One] Full Article

CLINICAL RESEARCH

Intermittent versus Continuous Androgen Deprivation in Prostate Cancer
Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. Researchers aimed to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival. [New Engl J Med] Abstract

Impact of ¹⁸F-Choline PET/CT in Prostate Cancer Patients with Biochemical Recurrence: Influence of Androgen Deprivation Therapy and Correlation with PSA Kinetics
Researchers evaluated the potential of ¹⁸F-fluoromethyldimethyl-2-hydroxyethyl-ammonium (FCH) PET/CT in the detection of recurrent disease or distant metastases and correlated its diagnostic accuracy with prostate-specific antigen (PSA) levels in prostate cancer patients with biochemical evidence of recurrence. ¹⁸F-FCH PET/CT was able to correctly detect malignant lesions in 74% of patients but was negative in 26%. [J Nucl Med] Abstract

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CureVac Initiates Phase IIb Clinical Trial of its mRNA-Based Cancer Vaccine in Patients with Castration-Resistant Prostate Cancer
CureVac GmbH, announced that it has initiated a double-blind, randomized Phase IIb clinical trial of its RNActive® cancer vaccine, CV9104, for the treatment of patients with castration-resistant prostate cancer. [CureVac GmbH] Press Release

Chesapeake Urology Associates Launches Prostate Cancer Website
Chesapeake Urology Associates has launched a comprehensive website devoted strictly to its Prostate Cancer Care Program. The site is an easy-to-access body of information that was built for prostate cancer patients and consumers alike. [PR Newswire Association LLC] Press Release

Largest Men’s Health Event Series In U.S. Formed, Kicks Off April 27
More than 60 events nationwide have united under the same banner for one cause. Called the ZERO Prostate Cancer Challenge, the new series is comprised of run/walks, golf tournaments and teams at top endurance events. [ZERO] Press Release

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)

NEW Cold Spring Harbor: Mouse Development, Stem Cells & Cancer
June 5-25, 2013
Cold Spring Harbor, United States

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

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

PhD Studentship – Detection of Novel Prostate Cancer Biomarkers (University of Bath)

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)

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