Mammary Cell News Volume 8.00 | Jan 7 2016

Therapeutic Targeting of Casein Kinase 1δ in Breast Cancer
Researchers demonstrated that CSNK1D is amplified and/or overexpressed in human breast tumors and that casein kinase 1δ is a vulnerability of human breast cancer subtypes overexpressing this kinase. [Sci Transl Med] Abstract | Press Release

Proteomic Maps of Breast Cancer Subtypes
Scientists analyzed 40 estrogen receptor positive (luminal), Her2 positive and triple negative breast tumors and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell-cell communication. [Nat Commun] Full Article

Combination OX40 Agonism/CTLA-4 Blockade with HER2 Vaccination Reverses T-Cell Anergy and Promotes Survival in Tumor-Bearing Mice
Investigators demonstrated that dual aOX40 anti-CD134/anti-cytotoxic T-lymphocyte-associated protein 4 immunotherapy generated a potent antigen-specific CD8 T-cell response, enhancing expansion, effector function, and memory T-cell persistence. [Proc Natl Acad Sci USA] Abstract | Full Article

PMCA2 Regulates HER2 Protein Kinase Localization and Signaling and Promotes HER2-Mediated Breast Cancer
The authors found that plasma membrane calcium ATPase2 (PMCA2) expression correlates with human epidermal growth factor receptor 2 (HER2) levels in breast cancers and that PMCA2 interacts with HER2 in specific actin-rich membrane domains. Knocking down PMCA2 increases intracellular calcium, disrupts interactions between HER2 and HSP-90, inhibits HER2 signaling, and results in internalization and degradation of HER2. [Proc Natl Acad Sci USA] Abstract | Full Article

HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediates Transcriptional Activation by c-Myc
Among 388 c-Myc target genes in human MCF-7 breast cancer cells, researchers found that their promoters could be occupied by the oncoprotein HBXIP. Clinical breast tumor specimens confirmed that the HBXIP expression correlated with expression of the c-Myc target genes Cyclin A, eIF4E and LDHA. [Cancer Res] Abstract

Tumor Suppressor Control of the Cancer Stem Cell Niche
To determine whether proliferator activated receptor γ (PPARγ) regulates mammary stem cells (MSC) expansion in mammary cancer, the authors deleted PPARγ expression in the mammary epithelium of an in vivo model of basal breast cancer. Loss of PPARγ expression reduced tumor latency, and expanded the CD24⁺/CD49f^hi MSC population. [Oncogene] Abstract

HER2 Induced EMT and Tumorigenicity in Breast Epithelial Progenitor Cells Is Inhibited by Coexpression of EGFR
Researchers showed that overexpression of HER2 in D492 (D492^HER2) resulted in epithelial to mesenchyme transition (EMT), loss of contact growth inhibition and increased oncogenic potential in vivo. HER2 overexpression, furthermore, inhibited endogenous epidermal growth factor receptor (EGFR) expression. [Oncogene] Full Article

The Ubiquitin Ligase Smurf2 Suppresses TGFβ-Induced Epithelial–Mesenchymal Transition in a Sumoylation-Regulated Manner
The authors report that knockdown of the ubiquitin ligase Smurf2 promotes the ability of transforming growth factor-β (TGFβ) to induce epithelial–mesenchymal transition in a three-dimensional cell culture model of NMuMG mammary epithelial cells. [Cell Death Differ] Abstract

Valproic Acid Potentiates the Anticancer Activity of Capecitabine In Vitro and In Vivo in Breast Cancer Models via Induction of Thymidine Phosphorylase Expression
The authors demonstrated that histone deacetylase inhibitors, including low anticonvulsant dosage of valproic acid, induced the dose- and time-dependent up-regulation of thymidine phosphorylase transcript and protein expression in breast cancer cells, but not in the non-tumorigenic breast MCF-10A cell line. [Oncotarget] Abstract | Full Article 

A New Hexapeptide from the Leader Peptide of rMnSOD Enters Cells through the Estrogen Receptor to Deliver Therapeutic Molecules
A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Researchers demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the estrogen receptor. [Sci Rep] Full Article

Overexpression of HER-2 in MDA-MB-435/LCC6 Tumors Is Associated with Higher Metabolic Activity and Lower Energy Stress
To further evaluate factors responsible for HER-2-associated changes in the tumor microenvironment, small animal magnetic resonance imaging and positron emission tomography were used to measure tumor tissue perfusion and metabolism, respectively. [Sci Rep] Full Article

CLINICAL RESEARCH

Ovarian Suppression with Triptorelin during Adjuvant Breast Cancer Chemotherapy and Long-Term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial
Investigators evaluated long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. [JAMA] Abstract | Press Release

Twelve-Month Estrogen Levels in Premenopausal Women with Hormone Receptor-Positive Breast Cancer Receiving Adjuvant Triptorelin plus Exemestane or Tamoxifen in the Suppression of Ovarian Function Trial (SOFT): The SOFT-EST Substudy
Premenopausal patients with early breast cancer on the Suppression of Ovarian Function Trial who selected triptorelin as the ovarian suppression method and were randomly assigned to exemestane plus triptorelin or tamoxifen plus triptorelin were enrolled until the target population of 120 patients was reached. [J Clin Oncol] Abstract | Full Article

3D Scaffolds in Breast Cancer Research
This review focuses on the most recent advances in scaffolding techniques, the cell-extracellular matrix (ECM) and cell-cell interactions in scaffold cultures, the distinct physical properties and signaling regulation of cancer cell growth within the scaffolds, the sensitivities of the cancer cells to drugs in 3-dimentional culture, and the use of scaffolds for drug delivery into tumors. [Biomaterials] Abstract

Visit our reviews page to see a complete list of reviews in the mammary cell research field.

Gamma Medica and Alpha Imaging Partner and Sign Distribution Agreement
Alpha Imaging announced that it has executed a distribution agreement with Gamma Medica, Inc. The agreement covers distribution of Gamma Medica’s LumaGEM Molecular Breast Imaging solution in the Midwest and Mid-Atlantic regions. [Gamma Medica, Inc.] Press Release

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NEW Post-Doc Fellowship – Epidemiologist (German Cancer Research Center)

NEW PhD Studentships – Various Projects (University of Cambridge)

Postdoctoral Researcher – Breast Tumor Image Analysis (Institute of Cancer Research)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

PhD Researcher – Cancer Signaling/Epigenetics/Tumor Biology (Institut Curie)

PhD Researcher – Personalized Immunotherapy for Cancer (ISPIC Consortium Members)

Postdoctoral Researcher – HIF-Mediated Alternative Splicing in Cancer (ETH Zurich)

Cancer Biologist – (Wake Forest Baptist School of Medicine)

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