A5057456019- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Sarcoma Diagnosis and Treatment
- Cancer Cells and Metastasis
- FOXO transcription factor regulation
- RNA Research and Splicing
- Tumors and Oncological Cases
- Epigenetics and DNA Methylation
- Prostate Cancer Diagnosis and Treatment
- Bone Tumor Diagnosis and Treatments
- RNA modifications and cancer
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Cancer, Lipids, and Metabolism
- Virus-based gene therapy research
- Nuclear Receptors and Signaling
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Glutathione Transferases and Polymorphisms
- Histiocytic Disorders and Treatments
- Cancer Mechanisms and Therapy
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Bioactive Compounds and Antitumor Agents
Pfizer (United States)
2023
University of British Columbia
2008-2021
Vancouver General Hospital
2021
University of Calgary
2008-2020
Welsh Government
2017
Child and Family Research Institute
2009-2014
BC Cancer Agency
2010
Heinrich Heine University Düsseldorf
2010
Wake Forest University
2010
Center of Advanced European Studies and Research
2010
Abstract Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences treatment-induced suppression androgen receptor (AR), remain elusive. Using a unique model AR pathway inhibitor–resistant cancer, we identified AR-dependent control neural transcription factor BRN2 (encoded by POU3F2) as major driver NEPC and aggressive tumor growth, both in vitro vivo. Mechanistic studies showed directly suppresses transcription, which is...
Abstract Treatment with androgen receptor pathway inhibitors (ARPIs) in prostate cancer leads to the emergence of resistant tumors characterized by lineage plasticity and differentiation toward neuroendocrine lineage. Here, we find that ARPIs induce a rapid epigenetic alteration mediated large-scale chromatin remodeling support activation stem/neuronal transcriptional programs. We identify proneuronal transcription factor ASCL1 motif be enriched hyper-accessible regions. acts as driver...
Abstract Background The Prolactin ( PRL ) hormone gene family shows considerable variation among placental mammals. Whereas there is a single in humans that expressed by the pituitary, are an additional 22 genes mice including lactogens (PL) and Prolactin-related proteins (PLPs) whose expression limited to placenta. To understand regulation potential functions of these genes, we conducted detailed temporal spatial study placenta between embryonic days 7.5 E18.5 three genetic strains. Results...
Abstract Y-box binding protein-1 (YB-1) is an oncogenic transcription/translation factor expressed in >40% of breast cancers, where it associated with poor prognosis, disease recurrence, and drug resistance. We questioned whether this may be linked to the ability YB-1 induce expression genes cancer stem cells such as CD44 CD49f. Herein, we report that binds CD49f promoters transcriptionally upregulate their expressions. The introduction wild-type (WT) or activated P-YB-1S102...
Basal-like breast cancers (BLBC) frequently overexpress the epidermal growth factor receptor (EGFR) and subsequently have high levels of signaling through MAP kinase pathway, which is thought to contribute their aggressive behavior. While we previously reported expression Y-box binding protein-1 (YB-1) in 73% BLBC, it unclear whether can be regulated by a component pathway. Phosphorylation YB-1 at serine 102 residue required for transcriptional activation growth-enhancing genes, such as...
Abstract Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we perform CRISPRi screens of 260 rCREs PCa cell lines. We find that harboring high risk more essential for proliferation H3K27ac occupancy is a strong indicator essentiality. also show cell-line-specific the 8q24.21 region, with rs11986220-containing rCRE regulating MYC PVT1 expression, tumorigenesis manner,...
Abstract Rhabdomyosarcoma, consisting of alveolar (aRMS) and embryonal (eRMS) subtypes, is the most common type sarcoma in children. Currently, there are no targeted drug therapies available for rhabdomyosarcoma. In searching new molecular therapeutic targets, we carried out genome-wide small interfering RNA (siRNA) library screens targeting human phosphatases (n = 206) kinases 691) initially against an aRMS cell line, RH30. Sixteen 50 were identified based on growth inhibition after 72...
There is growing evidence that cancer-initiation could result from epigenetic changes. Y-box binding protein-1 (YB-1) a transcription/translation factor promotes the formation of tumors in transgenic mice; however, underlying molecular events are not understood. To explore this human model system, YB-1 was expressed mammary epithelial cells under control tetracycline-inducible promoter. The induction promoted phenotypes associated with malignancy three-dimensional breast acini cultures. This...
Abstract Purpose: Prostate cancer was recently classified to three clinically relevant subtypes (PCS) demarcated by unique pathway activation and clinical aggressiveness. In this preclinical study, we investigated molecular targets therapeutics for PCS1, the most aggressive lethal subtype, with no treatment options available in clinic. Experimental Design: We utilized PCS1 gene set our model of enzalutamide (ENZR) castration-resistant prostate (CRPC) identify targetable pathways inhibitors...
// Alastair H. Davies 1 , Kristen Reipas 2 Kaiji Hu 3 Rachel Berns Natalie Firmino Anna L. Stratford and Sandra E. Dunn 4 Department of Urological Sciences, Vancouver Prostate Centre, Vancouver, BC, Canada School Medicine, Queen's University, Kingston, ON, Pediatrics, Child Family Research Institute, University British Columbia, Phoenix Molecular Diagnostics, Richmond, Correspondence to: Dunn, email: Keywords : RSK, YB-1, drug resistance, target, cancer stem cells, breast Received April 20,...
The major milestones in mouse placental development are well described, but our understanding is limited to how the placenta can adapt damage or changes environment. By using stereology and expression of cell cycle markers, we found that grows under normal conditions not just by hyperplasia trophoblast cells also through extensive polyploidy hypertrophy. In response feeding a low protein diet mothers prior during pregnancy, mimic chronic malnutrition, this program was altered it influenced...
Alastair H. Davies and Sandra E. Dunn 1 Laboratory of Oncogenomic Research, Departments Pediatrics Experimental Medicine, Child Family Research Institute, University British Columbia, Vancouver, BC, V5Z 4H4, Canada Keywords: YB-1, HER2, RSK, MAPK signaling, pre-malignancy, Kinex antibody microarray Received: April 21, 2011; Accepted: May 13, Published: Correspondence: Dunn, e-mail: // Abstract Surprisingly little is known about the underlying genetic events that trigger progression a normal...
Androgens are a major driver of prostate cancer (PCa) and continue to be critical treatment target for advanced disease, which includes castration therapy antiandrogens. However, resistance these therapies leading metastatic castration-resistant (mCRPC), the emergence treatment-induced neuroendocrine disease (tNEPC) remains an ongoing challenge. Instability DNA methylome is well established as hallmark PCa development progression. Therefore, investigating dynamics methylation changes going...