Mammary Cell News Volume 5.21 | May 30 2013

LABORATORY RESEARCH

HMGA2/TET1/HOXA9 Signaling Pathway Regulates Breast Cancer Growth and Metastasis
Scientists identified upstream activators and downstream effectors of ten-eleven translocation 1 (TET1) in breast cancer using human breast cancer cells and a genetically engineered mouse model. They showed that depleting the architectural transcription factor high mobility group AT-hook 2 (HMGA2) induces TET1. TET1 binds and demethylates its own promoter and the promoter of homeobox A (HOXA) genes, enhancing its own expression and stimulating expression of HOXA genes including HOXA7 and HOXA9. [Proc Natl Acad Sci USA] Abstract

The Polycomb Group Gene Ezh2 Regulates Mammary Gland Morphogenesis and Maintains the Luminal Progenitor Pool
In order to investigate the role of EZH2 in normal mammary gland epithelium, investigators generated novel transgenic mice that express doxycycline-regulatable shRNAs directed against Ezh2. Knockdown of EZH2 resulted in delayed outgrowth of the mammary epithelium during puberty, due to impaired terminal end bud formation and ductal elongation. [Stem Cells] Abstract

Role of Nek2 on Centrosome Duplication and Aneuploidy in Breast Cancer Cells
To identify the molecules important in breast cancer progression and metastasis, researchers tested the in vivo effects of inhibiting the functions of various kinases and genes involved in the regulation/modulation of the cytoskeleton by downregulating them in mouse PyMT mammary tumor cells and human breast cancer cell lines. [Oncogene] Abstract

SWI/SNF Chromatin-Remodeling Factor Smarcd3/Baf60c Controls EMT by Inducing Wnt5a Signaling
The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of Claudin-low triple negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced epithelial-mesenchymal transition (EMT). [Mol Cell Biol] Abstract

Directing HER4 mRNA Expression towards the CYT2 Isoform by Antisense Oligonucleotide Decreases Growth of Breast Cancer Cells In Vitro and In Vivo
Investigators used a splice-switching oligonucleotide (SSO) to direct the alternative splicing of HER4 from the CYT1 to the CYT2 isoform in HER4-expressing breast cancer cells. Treatment with a target-specific SSO was accompanied by a decreased growth of the cells. [Brit J Cancer] Abstract

FOXP3-Positive Regulatory T Lymphocytes and Epithelial FOXP3 Expression in Synchronous Normal, Ductal Carcinoma In Situ, and Invasive Cancer of the Breast
Scientists evaluated quantitative FOXP3 expression in lymphocytes as well as in epithelial cells in a set of thirty-two breast tumors with synchronous normal epithelium, ductal carcinoma in situ, and invasive ductal carcinoma components. [Breast Cancer Res Treat] Abstract

P190B RhoGAP Overexpression in the Developing Mammary Epithelium Induces TGFβ-Dependent Fibroblast Activation
The authors hypothesized that mammary epithelial cell (MEC) overexpression of p190B regulates paracrine interactions to impact fibroblast activation. Using a combination of in vivo morphometric and immunohistochemical analyses and primary cell culture assays, they found that p190B overexpression in MECs activates fibroblasts leading to increased collagen, fibronectin, and laminin production and elevated expression of the collagen crosslinking enzyme lysyl oxidase. [PLoS One] Full Article

Role of SMC1 in Overcoming Drug Resistance in Triple Negative Breast Cancer
Data showed that structural maintenance of chromosome 1 (SMC1), a subunit of the cohesin protein complex, is differentially overexpressed both at RNA and protein level in a panel of triple-negative breast cancer  (TNBC) cell lines as compared to normal epithelial or luminal breast cancer cells, suggesting that the amplified product of this normal gene may play role in tumorigenesis in TNBC. [PLoS One] Full Article

Antiandrogenic Actions of Medroxyprogesterone Acetate on Epithelial Cells within Normal Human Breast Tissues Cultured Ex Vivo
Researchers investigated the potential of medroxyprogesterone acetate to disrupt androgen receptor (AR) signaling in an ex vivo culture model of normal human breast tissue. [Menopause] Abstract

CLINICAL RESEARCH

A Randomized, Double-Blind, Controlled Study of Exemestane versus Anastrozole for the First-Line Treatment of Postmenopausal Japanese Women with Hormone-Receptor-Positive Advanced Breast Cancer
The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced, hormone-receptor-positive breast cancer. This phase III, randomized, double-blind study directly compared time to progression for exemestane and anastrozole therapy in this patient population. [Breast Cancer Res Treat] Abstract

CYP2D6 Polymorphisms Influence Tamoxifen Treatment Outcomes in Breast Cancer Patients: A Meta-Analysis
Researchers evaluated whether breast cancer patients with CYP2D6 gene variation have different clinical tamoxifen treatment outcomes compared to those with normal function of CYP2D6. [Cancer Chemother Pharmacol] Abstract

New Alliance for European Excellence and Competitiveness in Life Sciences
At the Centre for Genomic Regulation, in Barcelona, directors and staff from ten top European research institutes will kick off a new alliance, called EU-LIFE, that will promote European research. The mission of EU-LIFE is to foster excellence, share knowledge, and influence policies in life sciences. [VIB] Press Release

ROI Requests Research Proposals to Examine the Comparative Value of Radiation Therapy
The Radiation Oncology Institute (ROI) is seeking proposals to examine the comparative value of radiation therapy and will provide support for the research project in the amount of $200,000 over two years. [Newswise, Inc.] Press Release

Stem Cell Agency Awards More than $42 Million in New Research and Leadership Funding
California’s position as a global leader in stem cell research has been strengthened by the awarding of $36 million in funds to attract six world-class scientists to the state, and more than $6 million to create a partnership with Sangamo BioSciences to develop a therapy for beta-thalassemia. [California Institute for Regenerative Medicine] Press Release

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NEW American Association for Cancer Research (AACR): Frontiers in Basic Cancer Research
September 18-22, 2013
National Harbor, United States

Visit our events page to see a complete list of events in the mammary cell community.

NEW Postdoctoral Position – Breast Cancer/Stem Cell Biology (UC College of Medicine)

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

Postdoctoral Fellow – Cancer Genes in Breast Cancer (MD Anderson Cancer Center)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Fellow – Breast Cancer Research (Weizmann Institute of Science)

Postdoctoral Fellow – Breast Cancer Cell Research (Mount Sinai School of Medicine)

Research Associate – Breast Cancer Biology (University of North Carolina at Charlotte, Department of Biology)


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