Mammary Cell News Volume 5.20 | May 23 2013

LABORATORY RESEARCH

Dynamic Methylation of Numb by Set8 Regulates Its Binding to p53 and Apoptosis
Although Numb exhibits its tumor-suppressive function in breast cancer in part by binding to and stabilizing p53, it is unknown how the Numb-p53 interaction is regulated in cells. The authors found that Numb is methylated in its phosphotyrosine-binding domain by the lysine methyltransferase Set8. Moreover, methylation uncouples Numb from p53, resulting in increased p53 ubiquitination and degradation. [Mol Cell] Abstract | Press Release

Usp18 Deficient Mammary Epithelial Cells Create an Antitumor Environment Driven by Hypersensitivity to Interferon-λ and Elevated Secretion of Cxcl10
Using the PyVmT model of mammary tumorigenesis, researchers showed that lack of the Usp18 gene significantly inhibits tumor growth by creating a tumor-suppressive microenvironment. Generation of this antitumor environment is driven by elevated secretion of the potent T-cell chemoattractant Cxcl10 by Usp18 deficient mammary epithelial cells, which leads to recruitment of Th1 subtype CD4⁺ T cells. [EMBO Mol Med] Abstract

Regulation of FAK Activation, Breast Cancer Cell Motility and Amoeboid Invasion by the RhoA GEF Net1
Scientists showed that expression of both Net1 isoforms in breast cancer cells is required for efficient cell motility. Although loss of Net1 isoform expression only partially blocks RhoA activation, it inhibits LPA-stimulated migration as efficiently as knockdown of RhoA itself. [Mol Cell Biol] Abstract

Silencing the Mannose 6-Phosphate/IGF-II Receptor Differentially Affects Tumorigenic Properties of Normal Breast Epithelial Cells
Researchers investigated the impact of mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF-IIR) silencing using phenotypically normal (MCF-10A) and oncogenically transformed human breast epithelial cell lines as model systems. In both cell lines, silencing of M6P/IGF-IIR increased cell proliferation and motility, with the effects being more pronounced in MCF-10A cells. [Int J Cancer] Abstract

Progesterone Metabolites Regulate Induction, Growth and Suppression of Estrogen- and Progesterone Receptor-Negative Human Breast Cell Tumors
In vivo studies were conducted to investigate the ability of 5alphaP and 3alphaHP to control initiation, growth and regression of estrogen receptor (ER)/progesterone receptor (PR)-negative human breast cell tumors. ER/PR-negative human breast cells were implanted into mammary fat pads of immunosuppressed mice and the effects of 5alphaP and 3alphaHP treatments on tumor initiation, growth, suppression/regression and histopathology were assessed in five separate experiments. [Breast Cancer Res]
Abstract | Full Article | Press Release

RANKL/RANK/MMP-1 Molecular Triad Contributes to the Metastatic Phenotype of Breast and Prostate Cancer Cells In Vitro
To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype, the authors analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. [PLoS One]
Full Article

Dietary Chemopreventative Benzyl Isothiocyanate Inhibits Breast Cancer Stem Cells In Vitro and In Vivo
Scientists demonstrated the efficacy of benzyl isothiocyanate (BITC) against breast cancer stem cells in vitro and in vivo. Mammosphere formation frequency and CD44high/CD24low/ESA+ and/or ALDH1+ populations in cultured MCF-7 and SUM159 human breast cancer cells were decreased significantly in the presence of plasma achievable concentrations of BITC. [Cancer Prev Res] Abstract

Naringin Inhibits Growth Potential of Human Triple-Negative Breast Cancer Cells by Targeting β-Catenin Signaling Pathway
Triple-negative breast cancer (TNBC) cell lines-based in vitro and in vivo models were used to explore the anticancer effect and mechanism of naringin. Data demonstrated that naringin inhibited cell proliferation, and promoted cell apoptosis and G1 cycle arrest, accompanied by increased p21 and decreased survivin. [Toxicol Lett] Abstract

Human T47D Breast Cancer Cells with Tetracycline-Dependent ERβ Expression Reflect ERα/ERβ Ratios in Rat and Human Breast Tissue
T47D-ERβ breast cancer cells with tetracycline-dependent ERβ expression and constant ERα expression can be used to investigate effects of varying ERα/ERβ ratios on estrogen-induced cellular responses. Investigators defined conditions at which ERα/ERβ ratios in T47D-ERβ cells best mimic ERα/ERβ ratios in breast and other estrogen-sensitive tissues in vivo in rat as well as in human. [Toxicol In Vitro] Abstract

CLINICAL RESEARCH

Overdiagnosis in Breast Cancer Screening: The Importance of Length of Observation Period and Lead Time
The authors postulated a female population aged 50-79 with a similar age structure and age-specific breast cancer incidence as in England and Wales before the screening program. They then imposed a two-yearly screening program; screening women aged 50-69, to run for twenty years, with exponentially distributed lead time with an average of 40 months in screen-detected cancers. [Breast Cancer Res] Abstract | Full Article

Implementation of Breast Tomosynthesis in a Routine Screening Practice: An Observational Study
Scientists used verified practice- and outcome-related databases to compute and compare recall rates, biopsy rates, cancer detection rates, and positive predictive values for six radiologists who interpreted screening mammography studies without and with the use of tomosynthesis. [Am J Roentgenol]
Abstract | Press Release

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Hologic Receives FDA Approval for a New Low-Dose 3D Mammography (Breast Tomosynthesis) Solution for Breast Cancer Screening
Hologic, Inc. announced that the U.S. Food and Drug Administration (FDA) approved the use of Hologic’s new C-View 2D imaging software. C-View 2D images may now be used in place of the conventional 2D exposure previously required as part of a Hologic 3D mammography screening exam. [Hologic, Inc.]
Press Release

MacroGenics Announces Margetuximab (MGAH22) Phase I Data Presentation at ASCO; Initiates Phase II Clinical Study to Evaluate Activity of Margetuximab in Patients with Metastatic Breast Cancer
MacroGenics, Inc. announced that an abstract titled, “Phase I study of margetuximab, an Fc-modified chimeric monoclonal antibody (MAb), in patients with advanced solid tumors expressing the HER2 oncoprotein,” will be presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO). MacroGenics also announced that the first patient has received study drug in a Phase II clinical study evaluating margetuximab in patients with metastatic breast cancer. [MacroGenics, Inc.] Press Release

Maryland Stem Cell Research Commission Funds 31 New Research Proposals in FY 2013
The Maryland Stem Cell Research Commission has completed its review of the 171 applications received in response to its FY 2013 Requests for Applications. The board of directors of the Maryland Technology Development Corporation approved the Commission’s recommendation to fund 31 new proposals with the Maryland Stem Cell Research Fund’s $10.4 million FY2013 budget. [Maryland Stem Cell Research Fund] 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 14th International TNF Conference: Tumor Necrosis Factor 2013
July 7-10, 2013
Quebec City, Canada

NEW  5th Annual Molecular Dx: Cancer Drug Development
July 18-20, 2013
Boston, United States

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

NEW Postdoctoral Position – Breast Cancer Metastasis (Weizmann Institute of Science)

NEW Postdoctoral Fellow – Cancer Genes in Breast Cancer (MD Anderson Cancer Center)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Fellow – Breast Cancer Research (Weizmann Institute of Science)

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

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

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

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