Mammary Cell News Volume 6.41 | Oct 23 2014

Identification of Multipotent Mammary Stem Cells by Protein C Receptor Expression
Researchers demonstrate that protein C receptor (Procr), a novel Wnt target in the mammary gland, marks a unique population of multipotent mouse mammary stem cells . Procr-positive cells localize to the basal layer, exhibit epithelial-to-mesenchymal transition characteristics, and express low levels of basal keratins. [Nature] Abstract

Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis
Investigators report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC-Loading Complex and display cell-independent capacity to process precursor miRNAs into mature miRNAs. Exosomes derived from cells and sera of patients with breast cancer instigate nontumorigenic epithelial cells to form tumors in a Dicer-dependent manner. [Cancer Cell] Abstract | Editorial | Press Release

MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis
Researchers show that mesenchymal stem/stromal cells (MSCs) cause aberrant expression of microRNAs, which, led by microRNA-199a, provide breast cancer cells with enhanced cancer stem cell properties. They demonstrate that such MSC-deregulated microRNAs constitute a network that converges on and represses the expression of FOXP2, a forkhead transcription factor tightly associated with speech and language development. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release

Pluripotent Stem Cell miRNAs and Metastasis in Invasive Breast Cancer
Researchers determined whether microRNA (miRNA) for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome. [J Natl Cancer Inst] Abstract

TOPK Inhibitor Induces Complete Tumor Regression in Xenograft Models of Human Cancer through Inhibition of Cytokinesis
TOPK (T-lymphokine-activated killer cell-originated protein kinase) is highly and frequently transactivated in various cancer tissues, including lung and triple-negative breast cancers, and plays an indispensable role in the mitosis of cancer cells. The authors report the development of a potent TOPK inhibitor, OTS964, which inhibits TOPK kinase activity with high affinity and selectivity. [Sci Transl Med] Abstract | Press Release

Single-Cell Analyses of Transcriptional Heterogeneity during Drug Tolerance Transition in Cancer Cells by RNA Sequencing
Scientists performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. They show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. [Proc Natl Acad Sci USA] Abstract | Press Release | Video

Combined Deletion of Pten and p53 in Mammary Epithelium Accelerates Triple-Negative Breast Cancer with Dependency on eEF2K
Investigators show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MMTV-Cre, which targets basal/luminal progenitors. Combined Pten-p53 mutations accelerated formation of claudin-low, triple-negative-like breast cancer that exhibited hyper-activated AKT signaling and more mesenchymal features relative to Pten or p53 single-mutant tumors. [EMBO Mol Med] Full Article

Anatomical Localization of Progenitor Cells in Human Breast Tissue Reveals Enrichment of Uncommitted Cells within Immature Lobules
Scientists characterized the mammary progenitor cell hierarchy and identified the anatomic location of progenitor cells within human breast tissues. [Breast Cancer Res] Abstract | Full Article

Integrative Investigation on Breast Cancer in ER, PR and HER2-Defined Subgroups Using mRNA and miRNA Expression Profiling
Investigators explored the intrinsic differences among breast cancer subgroups defined by immunohistochemical expression of hormone receptors ER and PR as well as human epidermal growth factor receptor 2 (HER2) using the mRNA and miRNA expression profiles of 115 tumors. [Sci Rep] Full Article

Inhibition of Triple-Negative and Herceptin-Resistant Breast Cancer Cell Proliferation and Migration by Annexin A2 Antibodies
Researchers demonstrate that annexin A2 interacts with epidermal growth factor receptor (EGFR) at the cell surface and has an important role in cancer cell proliferation and migration by modulating EGFR functions.
[Br J Cancer] Abstract

CLINICAL RESEARCH

Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831
Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer were previously reported. Investigators now report the planned definitive overall survival results from this joint analysis along with updates on the disease-free survival end point. [J Clin Oncol] Abstract | Full Article | Press Release

Anastrozole versus Tamoxifen as Adjuvant Therapy for Japanese Postmenopausal Patients with Hormone-Responsive Breast Cancer: Efficacy Results of Long-Term Follow-Up Data from the N-SAS BC 03 Trial
Investigators report the follow-up efficacy results from the N-SAS BC 03 trial where anastrozole was compared with tamoxifen as adjuvant therapy in postmenopausal Japanese patients with hormone-responsive early breast cancer. [Breast Cancer Res Treat] Abstract

Triple-Negative Breast Cancer: Investigating Potential Molecular Therapeutic Target
The authors investigated the molecular alteration present in triple-negative breast cancer which could lead to the creation of new targeted therapies in the future, with the aim to counteract this disease in the most effective way. [Exp Opin Ther Targets] Abstract

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Researchers Use ScreenCell^® to Enrich Breast Cancer CTC Biomarkers
ScreenCell has entered into a collaborative study with the Jefferson Breast Care Center to evaluate the effectiveness of ScreenCell’s proprietary devices and protocols for enrichment of circulating tumor cells (CTCs) from peripheral blood. [ScreenCell (Business Wire)] Press Release

Breast Cancer Researcher to Study Personalized Treatment Using Multi-Hormone Combinations
Tan A. Ince, M.D., Ph.D., of the University of Miami’s Sylvester Comprehensive Cancer Center has received a $250,000 grant from the Breast Cancer Research Foundation to research personalized treatment of breast tumors with multi-hormone combinations. [University of Miami Miller School of Medicine] Press Release

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Postdoctoral Position – Novel DNA Damage Checkpoint Pathways and Variants in Potential Breast Cancer Genes (University of Copenhagen)

Postdoctoral Fellow – Breast Cancer (University of Texas Health Science Center at San Antonio)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

Postdoctoral Position – Breast Cancer Biology (UT Southwestern)

Postdoctoral Fellow – Breast Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Stem Cells and Breast Cancer (Albert Einstein College of Medicine)

Postdoctoral Positions – Cell Death of Normal Tissue Stem Cells (Sloan-Kettering Institute)

Postdoctoral Fellow – Breast Cancer Translational Research (University of Houston – College of Pharmacy)

Scientist – Mammary Cell Research (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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