Mammary Cell News Volume 6.05 | Feb 13 2014

EZH2 Expands Breast Stem Cells through Activation of NOTCH1 Signaling
Researchers identify an unrecognized Enhancer of Zeste Homolog 2 (EZH2)/NOTCH1 axis that controls breast tumor-initiating cells in triple-negative breast carcinomas. EZH2 overexpression increases NOTCH1 expression and signaling, and inhibition of NOTCH1 activity prevents EZH2-mediated stem cell expansion in nontumorigenic breast cells. [Proc Natl Acad Sci USA] Abstract

ß1 Integrin Inhibition Elicits a Prometastatic Switch through the TGFß-miR-200-ZEB Network in E-Cadherin-Positive Triple-Negative Breast Cancer
Researchers found that the loss of ß1 integrins attenuated breast tumor growth but markedly enhanced tumor cell dissemination to the lungs. When cultured in three-dimensional extracellular matrix scaffolds, antibodies that blocked ß1 integrin function or knockdown of ß1 switched the migratory behavior of human and mouse E-cadherin-positive triple-negative breast cancer cells from collective to single cell movement. [Sci Signal] Abstract

Intracellular Routing in Breast Cancer Cells of Streptavidin-Conjugated Trastuzumab Fab Fragments Linked to Biotinylated Doxorubicin-Functionalized Metal Chelating Polymers
To evaluate the cellular and nuclear uptake of trastuzumab Fab-streptavidin-biotin-metal-chelating polymer-doxorubicin (Dox), researchers incubated human epidermal growth factor receptor-2+ SK-BR-3 human breast cancer cells with the complexes saturated with stable In³⁺ and visualized their distribution by confocal fluorescence microscopy, monitoring the fluorescence of Dox. [Biomacromolecules]
Abstract | Graphical Abstract

Estradiol Stimulates Glucose Metabolism via 6-Phosphofructo-2-Kinase (PFKFB3)
Scientists demonstrated that PFKFB3 expression is highest in stage III lymph node metastases relative to normal breast tissues and that exposure of human MCF-7 breast cancer cells to estradiol causes a rapid increase in 14C-glucose uptake that is coincident with an induction of PFKFB3 mRNA, protein expression and the intracellular concentration of its product, fructose-2,6-bisphosphate. [J Biol Chem] Abstract

Differential ERa-Mediated Rapid Estrogenic Actions of Ginsenoside Rg1 and Estren in Human Breast Cancer MCF-7 Cells
Investigators addressed the differential abilities of Rg1 and estren in terms of the ability to activate estrogen receptor (ER) and the ability to induce ER translocation in MCF-7 cells. [J Steroid Biochem Mol Biol] Abstract

Cellular Responses of BRCA1-Defective and Triple-Negative Breast Cancer Cells and In Vitro BRCA1 Interactions Induced by Metallo-Intercalator Ruthenium(II) Complexes Containing Chloro-Substituted Phenylazopyridine
HCC1937 cells were significantly more sensitive to the ruthenium complexes than the MDA-MB-231 and MCF-7 cells. Treatment demonstrated a higher degree of cytotoxicity than cisplatin against all three cell lines. [BMC Cancer] Abstract | Full Article

GPER Functions as a Tumor Suppressor in MCF-7 and SK-BR-3 Breast Cancer Cells
The orphan, membrane-bound estrogen receptor (GPER)-specific agonist G-1 inhibited breast cancer cell proliferation in concentration-dependent manner via induction of the cell cycle arrest in M-phase, enhanced phosphorylation of histone 3 and cell apoptosis. [J Cancer Res Clin Oncol] Abstract

Human Sprouty1 Suppresses Growth, Migration, and Invasion in Human Breast Cancer Cells
Researchers demonstrated that in breast cancer cell lines, MDA-MB-231 and T47D, transfection-induced overexpression of human Sprouty1 reduced cell population, proliferation, and colony formation in vitro without affecting cell apoptosis. [Tumor Biol] Abstract

CLINICAL RESEARCH

The PAM50 Risk-of-Recurrence Score Predicts Risk for Late Distant Recurrence after Endocrine Therapy in Postmenopausal Women with Endocrine-Responsive Early Breast Cancer
Researchers assessed the prognostic value of the PAM50 risk-of-recurrence score on late distant recurrence in a large cohort of postmenopausal, endocrine-responsive breast cancer patients. [Clin Cancer Res] Abstract

A Randomized Phase III Study Comparing Pegylated Liposomal Doxorubicin with Capecitabine as First-Line Chemotherapy in Elderly Patients with Metastatic Breast Cancer: Results of the OMEGA Study of the Dutch Breast Cancer Research Group BOOG
Both pegylated liposomal doxorubicin and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with metastatic breast cancer, even in vulnerable patients or patients aged =75 years. [Ann Oncol] Abstract

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Syndax Announces NCI and FDA Reach Agreement on a Special Protocol Assessment (SPA) for the Phase III Trial of Entinostat in Patients with Advanced ER+ Breast Cancer
Syndax Pharmaceuticals, Inc. announced that the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) has reached a special protocol assessment agreement with the U.S. Food and Drug Administration (FDA) for the planned pivotal Phase III trial of entinostat in patients with advanced breast cancer. [Syndax Pharmaceuticals, Inc.] Press Release

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Studentship – Microtubules and End-Binding Proteins in Epithelial Remodeling and Breast Cancer Invasion (University of East Anglia)

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