Mammary Cell News Volume 8.09 | Mar 10 2016

G9a-Mediated Methylation of ERα Links the PHF20/MOF Histone Acetyltransferase Complex to Hormonal Gene Expression
Scientists showed that euchromatin histone methyltransferase 2 (G9a) functions as a coactivator of the endogenous estrogen receptor α (ERα) in breast cancer cells in a histone methylation-independent manner. [Nat Commun] Full Article

Genetic Suppression Reveals DNA Repair-Independent Antagonism between BRCA1 and COBRA1 in Mammary Gland Development
Scientists interrogated the functional interaction between BRCA1 and COBRA1 during mouse mammary gland development. Tissue-specific deletion of Cobra1 reduced mammary epithelial compartments and blocked ductal morphogenesis, alveologenesis and lactogenesis, demonstrating a pivotal role of COBRA1 in adult tissue development. [Nat Commun] Full Article

Rab11-FIP1C Is a Critical Negative Regulator in ErbB2-Mediated Mammary Tumor Progression
Scientists used ErbB2 mouse models of human breast cancer to investigate rab coupling protein (FIP1C) function in tumorigenesis. Doxycycline-induced expression of FIP1C in the MMTV-ErbB2 mouse model resulted in delayed mammary tumor progression. [Cancer Res] Abstract

Synergistic Activation of ERα by Estrogen and Prolactin in Breast Cancer Cells Requires Tyrosyl Phosphorylation of PAK1
Researchers showed that estrogen dependent PAK1 is activated through both the estrogen receptor α (ERα) and GPER1 membrane receptors. Estrogen-dependent activation of PAK1 required the phosphorylation of tyrosine residues by Etk/Bmx and protein kinase A (PKA) within an assembled signaling complex comprising pTyr-PAK1, Etk/Bmx, the heterotrimer G-protein subunits Gβ1, Gγ2 and/or Gγ5, PAK-associated guanine nucleotide exchange factor, and PKA. [Cancer Res] Abstract

Neither Epithelial nor Mesenchymal Circulating Tumor Cells Isolated from Breast Cancer Patients Are Tumorigenic in NOD-scid Il2rg^null Mice
Scientists investigated the tumorigenic potential of circulating EpCAM+ tumor cells from cryopreserved mobilized leukapheresis products obtained from three metastatic breast cancer patients in remission. [Sci Rep] Full Article

MYC Functions Are Specific in Biological Subtypes of Breast Cancer and Confers Resistance to Endocrine Therapy in Luminal Tumors
The authors hypothesised that the functional role of c-MYC differs between molecular subtypes of breast cancers. [Br J Cancer] Abstract

Epigenetic Suppression of Neprilysin Regulates Breast Cancer Invasion
Investigators asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT–PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. [Oncogenesis] Full Article

CLINICAL RESEARCH

Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer
Researchers investigated whether the efficacy of trastuzumab emtansine, an antibody-drug conjugate comprised of the cytotoxic agent DM1 linked to the HER2-targeted antibody trastuzumab, was correlated with expression of specific biomarkers in the Phase III EMILIA study. [Clin Cancer Res] Abstract | Full Article

Genetic Alterations of Triple Negative Breast Cancer by Targeted Next-Generation Sequencing and Correlation with Tumor Morphology
Researchers defined the genetic alterations in 39 triple negative breast cancers using a high-depth targeted massively parallel sequencing assay and correlated the findings with a detailed morphologic analysis. [Mod Pathol] Abstract

Initial Results of a Prospective Clinical Trial of ¹⁸F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers
Scientists hypothesized that Fluorine-18-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (¹⁸F-Fluciclovine) may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of ¹⁸F-Fluciclovine PET/CT in newly diagnosed advanced local invasive ductal carcinoma and invasive lobular carcinoma. [J Nucl Med] Abstract

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Celgene Notified of ANDA Filing for ABRAXANE^®
Celgene Corporation announced it has received a Paragraph IV Notice Letter advising that Actavis LLC submitted an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA) seeking authorization from the FDA to manufacture and market a generic version of ABRAXANE^®. [Celgene Corporation] Press Release

City of Hope, Israel Cancer Research Fund Create Program for Cancer Research
City of Hope and the Israel Cancer Research Fund (ICRF) announced the establishment of the Jacki and Bruce Barron Cancer Research Scholars’ Program that was made possible with a $5 million gift from The Harvey L. Miller Family Foundation. The new program will promote innovative and collaborative research, as well as the exchange of ideas and information between exceptional cancer researchers in the United States and Israel. [City of Hope (Business Wire)] Press Release

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European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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NEW Research Associate – Vascular Biology and Breast Cancer (University of South Australia)

NEW Postdoctoral Fellowship – Tumor Biology of Breast and Lung Cancer (Cold Spring Harbor Laboratory)

Research Technician – Breast Cancer (Kings College London)

Research Associate – Breast Cancer (University of Cambridge)

Postdoctoral Fellowship – Breast Cancer Stem Cells (Fundación para la Investigación Biosanitaria de Andalucia Oriental)

Postdoctoral Fellowship – Microenvironment of Breast Cancer (Icahn School of Medicine)

Postdoctoral Fellowship – Breast and Prostate Cancer Molecular Mechanisms (Feinberg School of Medicine)

Postdoctoral Fellowship – Epigenetic Reprogramming of Breast Cancer Stem Cells (University of Toronto)

Postdoctoral Fellowship – Various Projects in Cancer Biology (National University of Singapore)

Postdoctoral Fellowship – Genetic and Epigenetic Variability in Breast Cancer (The University of Tennessee Health Science Center)

Clinical Research Fellow – Breast Pathology (Institute of Cancer Research)

Pathologist – Breast/Gastrointestinal/Genitourinary Cancer (Beth Israel Deaconess Medical Center)

Manager – Medical and Breast Imaging (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellowship – Breast Cancer Biology (Washington University School of Medicine)

Clinical Pathways Associate – Cancer Therapeutics (Fred Hutchinson Cancer Research Center)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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