Mammary Cell News Volume 6.11 | Mar 27 2014

A Time- and Matrix-Dependent TGFBR3-JUND-KRT5 Regulatory Circuit in Single Breast Epithelial Cells and Basal-Like Premalignancies
In an immortalized basal-like breast epithelial cell line, researchers identified two anticorrelated gene-expression programs that arise among single extracellular matrix-attached cells during organotypic three-dimensional culture. [Nat Cell Biol] Abstract

Cytotoxicity of Paclitaxel in Breast Cancer Is due to Chromosome Missegregation on Multipolar Spindles
Scientists determined that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. [Sci Transl Med] Abstract

YB-1 Transforms Human Mammary Epithelial Cells through Chromatin Remodeling Leading to the Development of Basal-Like Breast Cancer
Y-box binding protein-1 (YB-1) was expressed in mammary epithelial cells under the control of a tetracycline-inducible promoter. The induction of YB-1 promoted phenotypes associated with malignancy in three-dimensional breast acini cultures. [Stem Cells] Abstract

Antagonism of EGFR and HER3 Enhances the Response to Inhibitors of the PI3K-Akt Pathway in Triple-Negative Breast Cancer
Researchers found that triple-negative breast cancer cell lines cultured with the epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 3 (HER3) ligand EGF or heregulin, respectively, and treated with either an Akt inhibitor or a phosphatidylinositol 3-kinase (PI3K) inhibitor had increased abundance and phosphorylation of HER3. [Sci Signal] Abstract

PDZ and LIM Domain Protein 1(PDLIM1)/CLP36 Promotes Breast Cancer Cell Migration, Invasion and Metastasis through Interaction with a-Actinin
Scientists showed that CLP36 is critical for promoting breast cancer cell migration and invasion in vitro and metastasis in vivo, whereas it is dispensable for breast cell proliferation and anchorage-independent growth in vitro and tumor growth in vivo. [Oncogene] Abstract

Fibroblast Growth Factor Receptor Splice Variants Are Stable Markers of Oncogenic Transforming Growth Factor- Beta1 Signaling in Metastatic Breast Cancers
Metastatic breast cancer cells undergo spontaneous downregulation of E-cadherin during primary tumor growth and its expression subsequently returns following initiation of metastatic outgrowth. [Breast Cancer Res] Abstract | Full Article

IRF-1 Regulates Alternative mRNA Splicing of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1) in Breast Epithelial Cells Generating an Immunoreceptor Tyrosine-Based Inhibition Motif (ITIM) Containing Isoform
Scientists provide evidence that CEACAM1’s promoter and variable exon 7 cross-talk allowing interferon regulatory factor-1 (IRF-1) to direct alternative splicing (AS) events. Transcriptome sequencing shows that IRF-1 can also induce the global AS of genes involved in regulation of growth and differentiation as well as genes of the cytokine family. [Mol Cancer] Abstract | Full Article

ERRß Signaling through FST and BCAS2 Inhibits Cellular Proliferation in Breast Cancer Cells
Overexpressed oestrogen-related receptor-ß (ERRß) induced Follistatin (FST)-mediated apoptosis in breast cancer cells, and E-cadherin expression was also enhanced through upregulation of FST. [Br J Cancer]
Full Article

Polyphenolics from Peach (Prunus persica var. Rich Lady) Inhibit Tumor Growth and Metastasis of MDA-MB-435 Breast Cancer Cells In Vivo
The tumor growth inhibition and anti-metastatic effects of peach polyphenolics were investigated in vivo using a xenograft model and MDA-MB-435 breast cancer cells. [J Nutr Biochem] Abstract | Press Release

Tea Polyphenols Induced Apoptosis of Breast Cancer Cells by Suppressing the Expression of Survivin
Researchers studied the mechanism of tea polyphenols (TP)-induced apoptosis of breast cancer cells. Cell proliferation was significantly inhibited by TP. [Sci Rep] Full Article

CLINICAL RESEARCH

Neoadjuvant and Adjuvant Trastuzumab in Patients with HER2-Positive Locally Advanced Breast Cancer (NOAH): Follow-Up of a Randomized Controlled Superiority Trial with a Parallel HER2-Negative Cohort
In a randomized, controlled, Phase III trial NeOAdjuvant Herceptin (NOAH) trial in women with HER2-positive locally advanced or inflammatory breast cancer, neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival. The authors report updated results from their primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy. [Lancet Oncol] Abstract

External Validity of a Trial Comprised of Elderly Patients with Hormone Receptor-Positive Breast Cancer
Researchers compared characteristics and outcomes of breast cancer patients who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population. [J Natl Cancer Inst] Abstract

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Adaptimmune Announces Award of £2.1 Million from the Biomedical Catalyst Fund
Adaptimmune announced that it has been awarded a grant of £2.1 million from the Biomedical Catalyst Fund, managed by the UK’s innovation agency the Technology Strategy Board and the Medical Research Council. The prestigious award will expedite the development of Adaptimmune’s second engineered T cell therapy program into the clinic in triple negative breast cancer. [Adaptimmune Limited] Press Release

$4.25 Million Grant Awarded to Rutgers Cancer Institute of New Jersey and University of Wisconsin Carbone Cancer Center to Develop Innovative Clinical Trials
Precision medicine, or the movement to ‘personalize’ cancer treatments, has grown significantly over the past few years, with researchers from large universities and cancer centers from across the nation making advances in identifying targeted therapies and understanding what drives them. Aiming to further build on that momentum with the development of innovative early-phase clinical trials examining genomic and therapeutic biomarkers is Robert S. DiPaola. [Rutgers Cancer Institute of New Jersey] Press Release

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Junior Faculty Position – Breast Pathology (Northwestern University)

Vice President, Global Medical Affairs – Breast Disease Lead (Celgene Corporation)

Research Assistant – Breast Epithelial Cell Research (Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

Postdoctoral Positions – Breast Cancer (Karolinska Institute)

Postdoctoral Fellow – Mechanisms that Contribute to Metastases of Breast Cancer Cells (Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai)

Postdoctoral Position – Functions of Epigenetic Enzymes in Breast Cancer (University of Wisconsin-Madison)

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

Postdoctoral Research Fellow (Brigham & Women’s Hospital and Harvard Medical School)

Scientific Communications & Publishing Coordinator (STEMCELL Technologies, Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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