Mammary Cell News Volume 5.23 | Jun 13 2013

Sox4 Is a Master Regulator of Epithelial-Mesenchymal Transition by Controlling Ezh2 Expression and Epigenetic Reprogramming
Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (EMT) in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 for gene repression. [Cancer Cell]
Abstract | Graphical Abstract | Press Release

LABORATORY RESEARCH

A Secreted PTEN Phosphatase that Enters Cells to Alter Signaling and Survival
Phosphatase and Tensin Homolog on chromosome Ten (PTEN)-Long is a membrane permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized phosphoinositide-3 kinase signaling and induced tumor cell death in vitro and in vivo. [Science] 
Abstract | Press Release

PDEF Promotes Luminal Differentiation and Acts as a Survival Factor for Estrogen Receptor-Positive Breast Cancer Cells
Researchers identified prostate-derived ETS factor (PDEF) as a mediator of mammary luminal epithelial lineage-specific gene expression and as a factor required for tumorigenesis in a subset of breast cancers. [Cancer Cell] Abstract

β-Catenin Signaling Is a Critical Event in ErbB2-Mediated Mammary Tumor Progression
By comparing the transcriptional profiles of ErbB2KI mammary tumors and human ERBB2-positive breast cancers, researchers demonstrated that ErbB2KI tumors possess molecular features of the basal subtype of ERBB2-positive human breast cancer, including activation of canonical β-catenin signaling. Inhibition of β-catenin-dependent signaling in ErbB2KI-derived tumor cells using RNA interference impaired tumor initiation and metastasis. [Cancer Res] Abstract

Phospholipase D (PLD) Drives Cell Invasion, Tumor Growth and Metastasis in a Human Breast Cancer Xenograph Model
The authors demonstrated that the PLD2 isoform, which was analyzed directly in the tumors, is crucial for cell invasion that contributes critically to the growth and development of breast tumors and lung metastases in vivo. [Oncogene] Full Article

Downregulation of miR-140 Promotes Cancer Stem Cell Formation in Basal-Like Early Stage Breast Cancer
Scientists find that microRNA (miR)-140 has a critical role in regulating stem cell signaling in normal breast epithelium and in ductal carcinoma in situ (DCIS). miRNA profiling of normal mammary stem cells and cancer stem-like cells from DCIS tumors revealed that miR-140 is significantly downregulated in cancer stem-like cells compared with normal stem cells, linking miR-140 and dysregulated stem cell circuitry. [Oncogene] Abstract

Epithelial Cell Differentiation Regulated by MicroRNA-200a in Mammary Glands
Investigators found that one microRNA (miRNA), miR-200a, was relatively highly expressed in epithelial cell-rich organs such as mammary glands, lung, and kidney in mice. In mammary glands, miR-200a expression increased during mid-pregnancy through lactation; its expression was stimulated by lactogenic hormone treatment of mammary epithelial cells. [PLoS One] Full Article

GEP100 Regulates Epidermal Growth Factor-Induced MDA-MB-231 Breast Cancer Cell Invasion through the Activation of Arf6/ERK/uPAR Signaling Pathway
The authors found that down-regulation of endogenous GEP100 in MDA-MB-231 cells significantly inhibited epidermal growth factor (EGF)-induced cell invasion, which was rescued by over-expression of ectopic GEP100. EGF increased Arf6 activity, ERK phosphorylation, and uPAR expression in a time dependent manner. [Exp Cell Res] Abstract

CLINICAL RESEARCH

Breast Cancer Index Identifies Early Stage ER+ Breast Cancer Patients at Risk for Early and Late Distant Recurrence
Researchers examined the prognostic performance of an optimized model of Breast Cancer Index, an algorithmic gene expression-based signature, for prediction of early (0-5 years) and late (>5 years) risk of distant recurrence in estrogen receptor positive (ER+), lymph node negative patients. [Clin Cancer Res] Abstract

One Year of Adjuvant Tamoxifen Compared with Chemotherapy and Tamoxifen in Postmenopausal Patients with Stage II Breast Cancer
Investigators report the long-term results of a randomized trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil in postmenopausal high-risk breast cancer patients. In addition, they analyzed the prognostic and predictive value of centrally assessed subtypes. [Eur J Cancer] Abstract

Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) Levels in Patients with HER2-Positive Breast Cancer Receiving Chemotherapy with or without Trastuzumab: Results from North Central Cancer Treatment Group Adjuvant Trial N9831
The authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). [Cancer] Abstract

Funded by Volleyball Tournaments, Breast Cancer Pilot Study Succeeds
Funded by volleyball tournaments, a new study shows success in pinpointing individualized treatment for women with metastatic breast cancer. The pilot study is the first of its kind to utilize novel protein activation mapping technology along with the genomic fingerprint of cancer as a way to find the most effective treatment. [Press Release from George Mason University discussing research presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago]
Press Release | Abstract

MacroGenics Presents Phase I Data Showing Signs of Clinical Benefit for Margetuximab in HER2 Expressing Tumors; Phase II Clinical Trial Underway to Evaluate Activity in Patients with Advanced Breast Cancer
MacroGenics, Inc. announced that results of the first-in-human study of margetuximab. This open-label, multi-dose, single-arm, multi-center Phase I, dose-escalation study was conducted to define the toxicity profile, maximum tolerated dose, pharmacokinetics, immunogenicity, and potential anti-tumor activity of margetuximab in 34 patients with advanced HER2-positive breast cancer (2+ or 3+ by IHC) neoplasms, 23 of whom had breast cancer or gastroesophageal cancer. [Press release from MacroGenics, Inc. discussing research presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

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Generex Announces Interview of MD Anderson’s Dr. Elizabeth Mittendorf, Principal Investigator on Company’s AE37 Phase IIb Breast Cancer Efficacy Trial
Generex Biotechnology Corporation announced an interview given by Dr. Elizabeth Mittendorf, M.D., Ph.D.  Dr. Mittendorf is the Principal Investigator of the Company’s AE37 clinical trial to test the ability of the novel immunotherapeutic agent to prevent relapse in patients who have had HER2-expressing breast cancer, the largest Phase IIb peptide clinical trial conducted to date. [Generex Biotechnology Corporation]
Press Release

Tumor Immunotherapy Efficacy Increased in Both Breast and Prostate Cancer Preclinical Models with Addition of Galectin Inhibitor
Galectin Therapeutics announced that preclinical studies have shown that combining the galectin inhibitor GR-MD-02 with monoclonal antibodies that function as immune checkpoint blockade inhibitors enhance shrinkage of prostate and breast cancer tumors. [Galectin Therapeutics] Press Release

US Supreme Court Rules Patents on ‘Natural’ Human Genes Invalid
In one of the most anxiously awaited court decisions of the year, the US Supreme Court unanimously struck down patents on isolated, natural human genes. Patents on synthesized DNA, however, are still valid, the justices said. Included in that category are commercially important patents on cDNA – segments of DNA synthesized using an RNA template. [Supreme Court, United States] Press Release | Syllabus

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 American Association for Cancer Research (AACR) : Frontiers in Basic Cancer Research
September 18-22, 2013
National Harbor, United States

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

NEW Postdoctoral Position – lncRNA and RNA Binding Protein Interaction in Mammary Cancer Stem Cell (CIBIO, University of Trento)

PhD Studentship – Breast Cancer Biology (Royal College of Surgeons in Ireland)

Postdoctoral Position – Breast and Ovarian Cancer Biology (University of Pennsylvania School of Medicine)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Position – Breast Cancer/Stem Cell Biology (UC College of Medicine)

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

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 Cell Research (Mount Sinai School of Medicine)

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


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