Mammary Cell News Volume 6.04 | Feb 6 2014

Taxonomy of Breast Cancer Based on Normal Cell Phenotype Predicts Outcome
To provide a better definition of the subtypes of epithelial cells comprising the breast epithelium, researchers performed a systematic analysis of a large set of breast epithelial markers in more than 15,000 normal breast cells, which identified 11 differentiation states for normal luminal cells. [J Clin Invest] Full Article

shRNA Kinome Screen Identifies TBK1 as a Therapeutic Target for HER2⁺ Breast Cancer
Researchers showed that MMTV-Her2/Neu mammary tumor cells cultured as non-adherent spheres or as adherent monolayer cells select for stabilizing mutations in p53 that “immortalize” the cultures, and that after serial passages, sphere conditions maintain tumor-initiating cells whereas monolayer cells gradually lose these tumorigenic cells. [Cancer Res] Abstract

MDM2 Restrains Estrogen-Mediated AKT Activation by Promoting TBK1-Dependent HPIP Degradation
Scientists identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. [Cell Death Differ] Abstract

Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells
Researchers showed that, analogous to some normal stem cells, breast tumor initiating cells have distinct metabolic properties compared to non-tumorigenic cancer cells. [Stem Cells] Abstract

S-Nitrosation of Monocarboxylate Transporter 1: Inhibition of Pyruvate-Fueled Respiration and Proliferation of Breast Cancer Cells
Since several mitochondrial proteins are known to be targets of S-nitrosation, scientists determined whether bioenergetics are modulated by S-nitrosation and defined the subsequent effects on proliferation. The nitrosating agent S-nitroso-L-cysteine was used to initiate intracellular S-nitrosation, and treatment decreased mitochondrial function and inhibited proliferation of MCF7 mammary adenocarcinoma cells. [Free Radic Biol Med] Abstract

p53 Inactivation Decreases Dependence on Estrogen/ERK Signaling for Proliferation but Promotes EMT and Susceptibility to 3-Bromopyruvate in ERa⁺ Breast Cancer MCF-7 Cells
Researchers investigated whether p53 inactivation augments estrogen receptor alpha (ERa⁺) cell proliferation in response to restrictive estradiol, chemical MEK inhibition or metabolic inhibitors. [Biochem Pharmacol]
Full Article

Diallyl Trisulfide Inhibits Estrogen Receptor-a Activity in Human Breast Cancer Cells
This study reports that garlic organosulfide diallyl trisulfide inhibits estrogen receptor-a activity in human breast cancer cells. [Breast Cancer Res Treat] Abstract

Curcumin Inhibits Proliferation of Breast Cancer Cells through Nrf2-Mediated Down-Regulation of Fen1 Expression
Researchers demonstrated that curcumin inhibited Flap endonuclease 1 (Fen1)-dependent proliferation of MCF-7 cells and significantly induced Nrf2 protein expression while inhibiting Fen1 protein expression. [J Steroid Biochem Mol Biol] Abstract

TFPI1 Mediates Resistance to Doxorubicin in Breast Cancer Cells by Inducing a Hypoxic-Like Response
Scientists observed elevated HIF1a protein in Doxorubicin (DOX) resistant cells, and in cells with forced expression of Tissue Factor Pathway Inhibitor 1 (TFPI1), suggesting TFPI1 induces HIF1a. TFPI1 also induced c-MYC, c-SRC, and HDAC2 protein, as well as DOX resistance in parental cells. [PLoS One] Full Article

CLINICAL RESEARCH

Exposure-Response Relationship of T-DM1: Insight into Dose Optimization for Patients with HER2-Positive Metastatic Breast Cancer
Exposure-response analyses for ado-trastuzumab emtansine (T-DM1) were performed using data from a randomized, active-control trial in patients with HER2-positive metastatic breast cancer. [Clin Pharmacol Ther] Abstract

Limited Human Epidermal Growth Factor Receptor 2 Discordance in Metastatic Breast Cancer Patients Treated with Trastuzumab, a Population Based Study
Investigators assessed in a population based sample concordance of human epidermal growth factor receptor 2 (HER2) status in metastatic breast cancer patients locally tested HER2 positive and treated with trastuzumab. [Eur J Cancer] Abstract

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Iron Homeostasis in Breast Cancer
The authors summarize the basic mechanisms of systemic and cellular iron regulation and highlight the findings that link their deregulation with breast cancer. [Cancer Lett] Abstract

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AVEO and Astellas Discontinue Phase II Trial of Tivozanib in Breast Cancer
AVEO Oncology announced that AVEO and Astellas Pharma Inc. have jointly decided to discontinue the BATON (Biomarker Assessment of Tivozanib in ONcology) breast cancer clinical trial, a Phase II study in patients with locally recurrent or metastatic triple negative breast cancer, due to insufficient enrollment. [AVEO Oncology] Press Release

Oncothyreon and Array BioPharma Announce Initiation of Phase Ib Trial of ONT-380 in Combination with Capecitabine and/or Trastuzumab in Patients with Metastatic HER2+ Breast Cancer
Oncothyreon Inc. and Array BioPharma Inc. announced the initiation of a Phase Ib trial of ONT-380 in combination with Xeloda® and/or Herceptin® in patients with metastatic HER2+ breast cancer. [Oncothyreon Inc.] Press Release

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NEW Postdoctoral Fellow – Mechanisms that Contribute to Metastases of Breast Cancer Cells (Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai)

Clinical Research Fellow – Pathology (Institute of Cancer Research)

Postdoctoral Fellow – Hodgkin Lymphoma and Breast Cancer (Hackensack University Medical Center)

Postdoctoral Position – Functions of Epigenetic Enzymes in Breast Cancer (University of Wisconsin-Madison)

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

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

Postdoctoral Research Fellow (Brigham & Women’s Hospital and Harvard Medical School)

Postdoctoral Position – Stem Cells and Cancer (Brigham & Women’s Hospital – Harvard Medical School)

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