Mammary Cell News Volume 6.47 | Dec 4 2014

Repurposing of Bisphosphonates for the Prevention and Therapy of Nonsmall Cell Lung and Breast Cancer
Scientists show that bisphosphonates inhibit colony formation by HER1^ΔE746-A750-driven HCC827 nonsmall cell lung cancer and human epidermal growth factor receptor (HER)1^wt-expressing MB231 triple negative breast cancers, but not by HER^low-SW620 colon cancers. [Proc Natl Acad Sci USA] Abstract | Press Release

Hypoxia-Inducible Factors Are Required for Chemotherapy Resistance of Breast Cancer Stem Cells
Scientists demonstrate that hypoxia-inducible factor (HIF) expression and transcriptional activity are induced by treatment of breast cancer cell lines with paclitaxel or gemcitabine. Chemotherapy-induced HIF activity enriched the breast cancer stem cell population through interleukin-6 and interleukin-8 signaling and increased expression of multidrug resistance 1. [Proc Natl Acad Sci USA] Abstract | Full Article

KAP1 Promotes Proliferation and Metastatic Progression of Breast Cancer Cells
KAP1 silencing in breast cancer cells reduced proliferation and inhibited the growth and metastasis of tumor xenografts. Conversely, KAP1 overexpression stimulated cell proliferation and tumor growth. [Cancer Res] Abstract

LRH-1 Controls Proliferation in Breast Tumor Cells by Regulating CDKN1A Gene Expression
Scientists report that liver receptor homolog-1 (LRH-1) inhibition affects two- and three-dimensional cell proliferation of different types of breast cancer cells, including estrogen receptor α-positive and triple-negative cells. [Oncogene] Abstract

RUNX1, a Transcription Factor Mutated in Breast Cancer, Controls the Fate of ER-Positive Mammary Luminal Cells
Conditional knockout of Runx1 in mammary epithelial cells (MECs) by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. [eLife] Full Article

Cooperation between BRCA1 and Vitamin D Is Critical for Histone Acetylation of the p21waf1 Promoter and Growth Inhibition of Breast Cancer Cells and Cancer Stem-Like Cells
Scientists report that two non-calcemic analogues of 1α,25-dihydroxyvitamin D3 collaborate with BRCA1 in mediating growth inhibition of breast cancer cells and breast cancer stem-like cells. [Oncotarget] Full Article

Exosome-Mediated Transfer of miR-10b Promotes Cell Invasion in Breast Cancer
Scientists demonstrate that microRNA carrying exosomes can be transferred among different cell lines through direct uptake. miR-10b is highly expressed in metastatic breast cancer MDA-MB-231 cells as compared to non-metastatic breast cancer cells or non-malignant breast cells; it is actively secreted into medium via exosomes. [Mol Cancer] Abstract | Full Article

Combination Therapy Targeting Ectopic ATP Synthase and 26S Proteasome Induces ER Stress in Breast Cancer Cells
Scientists investigated the anticancer effects of the ATP synthase inhibitor citreoviridin on breast cancer cells through proteomic approaches and revealed that differentially expressed proteins in cell cycle regulation and in the unfolded protein response were functionally enriched. [Cell Death Dis] Full Article

MTDH Mediates Trastuzumab Resistance in HER2 Positive Breast Cancer by Decreasing PTEN Expression through an NFκB-Dependent Pathway
Since metadherin (MTDH) promotes malignant phenotype of breast cancer, investigators sought to define whether MTDH promotes trastuzumab resistance by decreasing chromosome 10 (PTEN) expression through an NFκB-dependent pathway. [BMC Cancer] Full Article

FOXD1 Promotes Breast Cancer Proliferation and Chemotherapeutic Drug Resistance by Targeting p27
Researchers found that FOXD1 is up-regulated in breast cancer tissues. Depletion of FOXD1 expression decreases the ability of cell proliferation and chemoresistance in MDA-MB-231 cells, whereas overexpression of FOXD1 increases the ability of cell proliferation and chemoresistance in MCF-7 cells. [Biochem Biophys Res Commun] Abstract

CLINICAL RESEARCH

Safety and Preliminary Evidence of Biologic Efficacy of a Mammaglobin-A DNA Vaccine in Patients with Stable Metastatic Breast Cancer
Fourteen subjects were treated with the Mammaglobin-A DNA vaccine and no significant adverse events have been observed. Eight of 14 subjects were HLA-A2⁺, and the CD8 T-cell response to vaccination was studied in detail. [Clin Cancer Res] Abstract | Press Release

Combination of Letrozole, Metronomic Cyclophosphamide and Sorafenib Is Well-Tolerated and Shows Activity in Patients with Primary Breast Cancer
Investigators assessed whether the combination of letrozole, metronomic cyclophosphamide and sorafenib is well tolerated and shows activity in primary breast cancer. [Br J Cancer] Abstract

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Puma Biotechnology Updates Timeline for Filing New Drug Application
Puma Biotechnology, Inc. provided an update on the timeline for filing its New Drug Application for the approval of PB272 (neratinib) in the extended adjuvant treatment of HER2-positive early stage breast cancer. [Puma Biotechnology, Inc.] Press Release

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)

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NEW Postdoctoral Fellow – Metastases of Breast Cancer Cells (Icahn School of Medicine at Mount Sinai)

NEW Research Technologist – Media Development (STEMCELL Technologies Inc.)

Postdoctoral Position – Molecular Mechanisms of Differentiation and Oncogenesis (University of Massachusetts Medical School)

Postdoctoral Researcher – Chromatin and Epigenetic Regulation (Van Andel Research Institute)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

Professor – Breast/Abdominal Surgery or Gynecology (Fudan University Shanghai Cancer Center)

Postdoctoral Fellow – Breast Cancer (University of Texas Health Science Center at San Antonio)

Scientist – Mammary Cell Research (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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