Mammary Cell News Volume 5.16 | Apr 25 2013

Notch2 Genetic Fate Mapping Reveals Two Previously Unrecognized Mammary Epithelial Lineages
Using conditional in vivo genetic labeling, scientists traced the fate of cells expressing the Notch2 receptor paralogue and uncovered the existence of two previously unrecognized mammary epithelial cell lineages that they term S and L. [Nat Cell Bio] Abstract

In Vivo NCL Targeting Affects Breast Cancer Aggressiveness through miRNA Regulation
The authors found that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of microRNAs (miRNAs), including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. [J Exp Med]
Abstract | Press Release

Inhibition of Redox/Fyn/c-Cbl Pathway Function by Cdc42 Controls Tumor Initiation Capacity and Tamoxifen Sensitivity in Basal-Like Breast Cancer Cells
Scientists found that basal-like breast cancer cells use Cdc42 to inhibit function of the redox/Fyn/c-Cbl pathway, which normally functions to convert small increases in oxidative status into enhanced degradation of c-Cbl target proteins. [EMBO Mol Med] Abstract | Press Release

Wnt/β-Catenin Pathway Represses let-7 MicroRNAs Expression via Transactivation of Lin28 to Augment Breast Cancer Stem Cell Expansion
Researchers identified Lin28, a negative let-7 biogenesis regulator, as a novel direct downstream target of Wnt/β-catenin pathway. Loss of function of Lin28 impairs the Wnt/β-catenin pathway-mediated let-7 inhibition and breast cancer stem cell expansion; enforced expression of let-7 blocks the Wnt/β-catenin pathway-stimulated breast cancer stem cell phenotype. [J Cell Sci] Abstract | Full Article

A Novel Monoclonal Antibody to Secreted Frizzled-Related Protein 2 Inhibits Tumor Growth
Scientists assessed the effects of secreted frizzled-related protein 2 (SFRP2) antagonism on tumor growth and Wnt-signaling and to evaluate whether SFRP2 is a viable therapeutic target. The antiangiogenic and antitumor properties of SFRP2 monoclonal antibody were assessed using in vitro proliferation, migration, tube formation assays, and in vivo angiosarcoma and triple-negative breast cancer models. [Mol Cancer Ther] Abstract | Press Release

Inhibition of the PI3K/AKT Pathway Potentiates Cytotoxicity of EGFR Kinase Inhibitors in Triple-Negative Breast Cancer Cells
The authors report that combinatorial treatment using epidermal growth factor receptor (EGFR) inhibitors, such as gefitinib or erlotinib, with PI3K/AKT pathway inhibitors demonstrated a synergistic, anti-proliferative effect in cell lines of the basal-like subtype, a subtype of triple-negative breast cancer. [J Cell Mol Med] Abstract

Expression Analysis of Rare Cellular Subsets: Direct RT-PCR on Limited Cell Numbers Obtained by FACS or Soft Agar Assays
Identification of transcriptional changes relevant to the tumorigenic potential of mammalian cells while they are actively growing as colonies in soft agar is hampered by limited amounts of starting material. Researchers describe a convenient method that fills the gap between single cell and whole tissue mRNA analysis, enabling mRNA quantification for individual colonies picked from soft agar. [Biotechniques] Abstract | Full Article

Radiation-Induced Senescence in Securin-Deficient Cancer Cells Promotes Cell Invasion Involving the IL-6/STAT3 and PDGF-BB/PDGFR Pathways
The authors previously showed that securin depletion promotes radiation-induced senescence and enhances radiosensitivity in human cancer cells. In this study, they showed that radiation induced senescence in securin-deficient human breast cancer cells involving the ATM/Chk2 and p38 pathways. [Sci Rep] Full Article

CLINICAL RESEARCH

Mammographic Density Reduction Is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients with Breast Cancer
Researchers discovered that women treated with tamoxifen who experienced a relative density reduction of more than 20% between baseline and first follow-up mammogram had a reduced risk of death as a result of breast cancer of 50% compared with women with stable mammographic density. [J Clin Oncol]
Abstract | Press Release

Relationship of Serum Estrogens and Estrogen Metabolites to Postmenopausal Breast Cancer Risk: A Nested Case-Control Study
A recently developed liquid chromatography tandem mass spectrometry-based method measuring a panel of 15 estrogen metabolites (EM) has been evaluated, linking high levels of 2-pathway metabolites relative to the parent estrogens to reduced breast cancer risk. The authors analyzed this panel of EM in a nested case-control study of postmenopausal breast cancer. [Breast Cancer Res] Abstract | Full Article

Low Serum Creatine Kinase Levels in Breast Cancer Patients: A Case-Control Study
This study aimed to investigate the role of serum creatine kinase (CK) level in breast cancer patients. 823 female patients diagnosed with breast cancer were consecutively recruited as cases, and 823 age-match patients with benign breast disease were selected as controls. Serum CK was analyzed by commercially available standardized methods. [PLoS One] Full Article

The Estrogen-Regulated Anterior Gradient 2 (AGR2) Protein in Breast Cancer: A Potential Drug Target and Biomarker
Initially discovered as an estrogen-responsive gene in breast cancer cell lines, AGR2 is a developmentally regulated gene belonging to the protein disulfide isomerase gene family. Developmentally, AGR2 is expressed in the mammary gland in an estrogen-dependent manner, and AGR2 knockout and overexpression mouse models indicate that the gene promotes lobuloalveolar development by stimulating cell proliferation. [Breast Cancer Res] Abstract

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Sareum Notified of Grant Award from UK Technology Strategy Board
Sareum is pleased to announce that it has received notification from the Technology Strategy Board that it has been offered a grant worth up to £150,000 from the Biomedical Catalyst. The grant will provide financial support for the Company’s Fatty Acid Synthase research program. Sareum has developed a novel chemical series which shows promising efficacy in breast cancer cell models. [Sareum Ltd.] Press Release

Provista Diagnostics, Inc. Is Pleased to Announce the Closing of a $6.0 Million Private Round of Series A Preferred Financing
Funding came from re-investment from many of the Company’s existing investors along with several new investors. The proceeds from the financing are to be used for prospective clinical trials for the Company’s dtectDx – Breast™ and additional product pipeline expansion, as well as general corporate purposes. [Provista Diagnostics, Inc.] Press Release

Indiana University Cancer Surgeon Looks to Greek Mythology for Inspiration in Nanoparticle Research
An Indiana University School of Medicine breast cancer surgeon is pursuing research that will utilize glass, gold, nanotechnology and Greek mythology hoping to vanquish breast cancer that has metastasized to the brain. Susan E. Clare, M.D., Ph.D. is the initiating principal investigator for a $573,000 Department of Defense grant that will allow her to explore a new approach to delivering therapy to brain metastases from primary breast cancer. [Indiana University] Press Release

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NEW Postdoctoral Fellow – Breast Cancer Cell Research (Mount Sinai School of Medicine)

NEW Research Associate (University of North Carolina at Charlotte, Department of Biology)

Postdoctoral Position – Establishing the Role of Key Recurring Genetic Mutations in Endocrine Resistant Breast Cancer (AstraZeneca)

Postdoctoral Position – Breast Cancer Research (Albert Einstein College Medicine)

Postdoctoral Position – Hypoxia Signaling, Prolyl Hydroxylases and Cancer (UNC-Chapel Hill)

Postdoctoral Position – Breast Cancer (UT Southwestern Medical Center at Dallas)

Product Director – Breast Marketing (Genomic Health)

Postdoctoral Position – Cancer Biology (Louisiana State University Health Science Center)

Postdoctoral Researcher – Cancer Genomics and Computational Biology/Bioinformatics (University of British Columbia/Provincial Health Services Authority)

Postdoctoral Position – Breast Cancer Signaling (Weizmann Institute of Science)


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