Volume 5.48 | Dec 5

Mammary Cell News 5.48 December 5, 2013
Mammary Cell News
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Cyclin D1 Induction of Dicer Governs MicroRNA Processing and Expression in Breast Cancer
Investigators showed that cyclin D1−/− cells are defective in pre-microRNA processing, which is restored by cyclin D1a rescue. Dicer is transcriptionally targeted by cyclin D1, via a cdk-independent mechanism. Cyclin D1 and Dicer expression significantly correlates in luminal A and basal-like subtypes of human breast cancer. [Nat Commun] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)

MiR-106b Expression Determines the Proliferation Paradox of TGF-β in Breast Cancer Cells
Scientists identified miR-106b as a molecular switch to determine TGF-β effects on cell proliferation. TGF-β1 enhances the transcription of miR-106b via a promoter independent of its host gene MCM7 by activating c-jun. [Oncogene] Abstract

Growth Arrest by the Antitumor Steroidal Lactone Withaferin A in Human Breast Cancer Cells Is Associated with Downregulation and Covalent Binding at Cysteine-303 of β-Tubulin
The authors report that tubulin is a novel target of Withaferin A (WA)-mediated growth arrest in human breast cancer cells. The G2 and mitotic arrest resulting from WA exposure in MCF-7, SUM159, and SK-BR-3 cells was associated with a marked decrease in protein levels of β-tubulin. [J Biol Chem] Abstract | Full Article

Prostaglandin E Receptor EP4 Is a Therapeutic Target in Breast Cancer Cells with Stem-Like Properties
Scientists showed that both prostaglandin E receptor 4 (EP4) and cyclooxygenase 2 (COX-2) are highly induced on candidate tumor-initiating/stem cell populations and that EP4 antagonists reduce cancer stem cell properties in vitro and in vivo supporting the hypothesis that EP4 and/or COX-2 may represent novel targets expressed by the most high risk and resistant subpopulations. [Breast Cancer Res Treat] Full Article

DNA-PK Inhibition by NU7441 Sensitizes Breast Cancer Cells to Ionizing Radiation and Doxorubicin
Researchers determined the cellular concentration of DNA-PK and other DSB-activated kinases: ATM and ATR and the effect of DNA-PK inhibition by NU7441 on DNA repair, cell cycle, and survival after ionizing radiation or doxorubicin treatment in three human breast cancer cell lines (MCF-7, MDA-MB-231, and T47D) representing different breast cancer subtypes. [Breast Cancer Res Treat] Abstract

β-Catenin, a Sox2 Binding Partner, Regulates the DNA Binding and Transcriptional Activity of Sox2 in Breast Cancer Cells
Using liquid chromatography-mass spectrometry and co-immunoprecipitation, the authors identified β-catenin as a Sox2 binding partner in MCF7 cells. The interaction between Sox2 and β-catenin was substantially different between the two cell subsets separated based on their differential responsiveness to a Sox2 reporter. [Cell Signal] Abstract

PPARγ-Inactive Δ2-Troglitazone Independently Triggers ER Stress and Apoptosis in Breast Cancer Cells
Investigators aimed to better understand peroxisome proliferator-activated receptor gamma (PPARγ)-independent pathways involved in anti-cancer effects of thiazolidinediones (TZDs). They focused on Δ2-troglitazone, a PPARγ inactive TZD that affects breast cancer cell viability. [Mol Carcinog] Abstract

STAT3 Activation in HER2-Overexpressing Breast Cancer Promotes Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits
Researchers showed that STAT3 was phosphorylated in HER2-overexpressing, ER-positive human breast tumors, and furthermore, phosphorylated STAT3 promoted the stem-like cell phenotype. [Int J Oncol] Abstract

Clofarabine, a Novel Adenosine Analogue, Reactivates DNA Methylation-Silenced Tumor Suppressor Genes and Inhibits Cell Growth in Breast Cancer Cells
Scientists investigated whether clofarabine influences methylation and expression of selected tumor suppressor genes, such as adenomatous polyposis coli, phosphatase and tensin homologue, and retinoic acid receptor beta 2, as well as expression of p53, p21 and DNA methyltransferase 1 in MCF-7 and MDA-MB-231 breast cancer cell lines with different invasive potential. [Eur J Pharmacol] Abstract


Comparison of Molecular Subtype Distribution in Triple-Negative Inflammatory and Non-Inflammatory Breast Cancers
The authors hypothesized that the distribution of triple-negative breast cancer (TNBC) subtypes differs between TN-inflammatory breast cancer (IBC) and TN-non-IBC. They determined the subtypes and compared clinical outcomes by subtype in TN-IBC and TN-non-IBC patients. [Breast Cancer Res] Abstract | Full Article

Breast Cancers with High DSS1 Expression that Potentially Maintains BRCA2 Stability Have Poor Prognosis in the Relapse-Free Survival
Genetic BRCA2 insufficiency is associated with breast cancer development; however, in sporadic breast cancer cases, high BRCA2 expression is paradoxically correlated with poor prognosis. Because DSS1, a mammalian component of the transcription/RNA export complex, is known to stabilize BRCA2, researchers investigated how the expression of DSS1 is associated with clinical parameters in breast cancers. [BMC Cancer] Abstract | Full Article

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Tackling the Diversity of Triple-Negative Breast Cancer
Triple-negative breast cancer comprises a highly diverse collection of cancers. The authors review this diversity both in terms of gene expression subtypes and the repertoire of genetic events. [Clin Cancer Res] Abstract

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Celldex Therapeutics Initiates METRIC, an Accelerated Approval Study of Glembatumumab Vedotin in Patients with Triple Negative Breast Cancer
Celldex Therapeutics, Inc. announced that it has launched a randomized study (METRIC) of Glembatumumab vedotin in patients with metastatic triple negative breast cancers that over-express glycoprotein NMB (gpNMB). Glembatumumab vedotin is an antibody-drug conjugate that targets and binds to gpNMB, a specific protein that is expressed in breast cancer that promotes the migration, invasion and metastasis of the disease. [Celldex Therapeutics, Inc.] Press Release

Medivation and Astellas Initiate Phase II Study of Enzalutamide in Advanced Breast Cancer that Is Estrogen or Progesterone Receptor Positive and HER2 Normal
Medivation, Inc. and Astellas Pharma US, Inc. announced the initiation of a Phase II clinical trial evaluating the safety and efficacy of enzalutamide in combination with exemestane in women with advanced breast cancer that is estrogen receptor positive or progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) normal. [Medivation, Inc.] Press Release

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Therapeutic Goods Administration (Australia)
NEW Beatson International Cancer Conference – Powering the Cancer Machine
July 6-9, 2014
Glasgow, Scotland

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NEW Clinical MD – Clinical Development Program for Oncology and Autoimmune Diseases (Immunomedics, Inc.)

NEW Chief Medical Officer – Novel Therapeutics in Oncology and Autoimmune Disease (Immunomedics, Inc.)

PhD Position – Integrated Classification of Breast Cancers to Optimize Treatment Protocols (Radboud University Nijmegen Medical Centre)

PhD Candidate – Wnt-Signaling and Stem Cell Biology in the Mammary Gland (University of Amsterdam)

Assistant, Associate, or Research Professor – Breast Cancer (Indiana University School of Medicine)

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

Postdoctoral Position – Computational Biology and Cancer Genomics (Albert Einstein College of Medicine)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

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