Mammary Cell News Volume 6.29 | Jul 31 2014

Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer
Light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. Researchers used a rat model of estrogen receptor MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. [Cancer Res] Abstract | Press Release

Nodal Signaling Promotes a Tumorigenic Phenotype in Human Breast Cancer
Scientists demonstrate that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic phenotypes both in vitro and in vivo. [Semin Cancer Biol] Abstract

TRIM24 Links Glucose Metabolism with Transformation of Human Mammary Epithelial Cells
Scientists used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and report that ectopic expression of tripartite motif 24 protein (TRIM24) in immortalized HMECs greatly increased cellular proliferation and induced malignant transformation. [Oncogene] Abstract

miR-7, Inhibited Indirectly by LincRNA HOTAIR, Directly Inhibits SETDB1 and Reverses the EMT of Breast Cancer Stem Cells by Downregulating the STAT3 Pathway
Researchers showed that miR-7, which was downregulated in breast cancer stem cells (BCSCs) isolated from the human MCF-7 and MDA-MB-231 cell lines, inhibited cell invasion and metastasis, decreased the BCSC population and partially reversed epithelial-mesenchymal transition (EMT) in MDA-MB-231 cells by directly targeting the oncogene, SETDB1. [Stem Cells] Abstract

MDM2-Mediated Degradation of SIRT6 Phosphorylated by AKT1 Promotes Tumorigenesis and Trastuzumab Resistance in Breast Cancer
Sirtuin 6 (SIRT6) is associated with longevity and is also a tumor suppressor. In various breast cancer cell lines, researchers demonstrate that SIRT6 was phosphorylated at Ser³³⁸ by the kinase AKT1, which induced the interaction and ubiquitination of SIRT6 by MDM2, targeting SIRT6 for protease-dependent degradation.
[Sci Signal] Abstract

Overexpression of Oct4 Suppresses the Metastatic Potential of Breast Cancer Cells via Rnd1 Downregulation
Researchers overexpressed and silenced Oct4 expression in two breast cancer cell lines, MDA-MB-231 and 4T1, separately. They showed that ectopic overexpression of Oct4 suppressed cell migration and invasion in vitro and the formation of metastatic lung nodules in vivo. Conversely, Oct4 downregulation increased the metastatic potential of breast cancer cells both in vitro and in vivo. [Biochim Biophys Acta] Abstract

Lymphatic Endothelial Cells Support Tumor Growth in Breast Cancer
Investigators co-injected endothelial cells with MDA-MB-231 breast cancer cells into animals and showed that lymphatic endothelial cells support tumor growth, human umbilical vein endothelial cells have no significant effect on tumor growth, whereas microvascular endothelial cells suppress it. [Sci Rep] Full Article

Critical Roles for Nitric Oxide and ERK in the Completion of Prosurvival Autophagy in 4OHTAM-Treated Estrogen Receptor-Positive Breast Cancer Cells
Autophagy is a mechanism of tamoxifen resistance in ER-positive (ER⁺) breast cancer cells. Investigators showed in ER⁺ MCF7 cells that 4-hydroxytamoxifen (4OHTAM) induced cellular nitric oxide (NO) that negatively regulates cellular superoxide and cytotoxicity and suggest an essential role for endogenous NO and ERK activation in the completion of pro-survival autophagy. [Cancer Lett] Abstract

Selective Androgen Receptor Modulators (SARMs) Negatively Regulate Triple-Negative Breast Cancer Growth and Epithelial: Mesenchymal Stem Cell Signaling
Researchers demonstrate that androgen receptor (AR) stimulation inhibits paracrine factors that are important for mesenchymal stem cell interactions and breast cancer invasion and metastasis and that SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer. [PLoS One] Full Article

CLINICAL RESEARCH

Androgen Receptor Expression in Male Breast Cancer Predicts Inferior Outcome and Poor Response to Tamoxifen Treatment
Scientists investigated the role of the androgen receptor (AR) in male breast cancer treatment and prognosis and to analyze the relationship between AR and the effect of tamoxifen treatment therapy in male breast cancer patients. [Eur J Endocrinol] Abstract

A Phase I Pharmacokinetics Study of Lapatinib and Tamoxifen in Metastatic Breast Cancer (EORTC 10053 Lapatam Study)
Researchers assessed the pharmacokinetic, tolerability, safety and preliminary clinical activity of tamoxifen and lapatinib in patients with metastatic breast cancer. [Breast] Abstract

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Clearview Diagnostics Receives NIH Grant to Develop Portable Ultrasound for Breast Cancer Screening
Clearview Diagnostics, Inc. announced the receipt of a grant from the National Institutes of Health (NIH) to develop a portable self-reading device for breast cancer screening.
[Clearview Diagnostics, Inc (PR Newswire Association LLC)] Press Release

Researchers to Study Mechanisms of Hard-to-Solve, Hereditary Breast Cancer to Find Treatment Option
Deborah Kelly and Zhi Sheng, assistant professors at the Virginia Tech Carilion Research Institute, recently received a grant from the Commonwealth Health Research Board to investigate hereditary breast cancer, an effort that may lead to new treatment approaches. The grant will fund a two-year project to study the mechanisms behind hereditary breast cancer related to the BRCA1 gene.
[Virginia Polytechnic Institute and State University] Press Release

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Postdoctoral Position – Triple Negative Breast Cancer (Weizmann Institute of Science)

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

Postdoctoral Fellow – Mammary Stem Cell Biology (University of Amsterdam)

Postdoctoral Fellow – Mammary Differentiation (University of British Columbia)

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

Postdoctoral Position – Breast Cancer Research (University of Oklahoma Health Sciences Center)

PhD Candidate – Mammary Stem Cell Biology (University of Amsterdam)

Postdoctoral Fellow – Breast Cancer Biology (University of Tennessee Health Science Center)

Postdoctoral Scholar – Cancer and RNA Research (Northwestern University)

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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