Mammary Cell News Volume 5.29 | Jul 25 2013

Activation-Induced Cytidine Deaminase (AID) Is Necessary for the Epithelial-Mesenchymal Transition in Mammary Epithelial Cells
Researchers find that expression of AID is induced by inflammatory signals that induce the epithelial to mesenchymal transition (EMT) in nontransformed mammary epithelial cells and in ZR75.1 breast cancer cells. shRNA-mediated knockdown of AID blocks induction of the EMT and prevents cells from acquiring invasive properties. [Proc Natl Acad Sci USA] Abstract

Ret Inhibition Decreases Growth and Metastatic Potential of Estrogen Receptor Positive Breast Cancer Cells
The role of Ret in ER+ breast cancer models was explored combining in vitro and in vivo approaches. The authors’ analyses revealed that ligand-induced Ret activation stimulates migration of breast cancer cells; rescues cells from anti-proliferative effects of endocrine treatment and stimulates expression of cytokines in the presence of endocrine agents. [EMBO Mol Med] Abstract

FER Kinase Promotes Breast Cancer Metastasis by Regulating α6- and β1-Integrin-Dependent Cell Adhesion and Anoikis Resistance
Investigators showed that FER kinase (FER) controls migration and metastasis of invasive human breast cancer cell lines by regulating α6- and β1-integrin-dependent adhesion. Conversely, the overexpression of FER in non-metastatic breast cancer cells induces pro-invasive features. [Oncogene] Full Article

BCL-2 Hypermethylation Is a Potential Biomarker of Sensitivity to Anti-Mitotic Chemotherapy in Endocrine-Resistant Breast Cancer
The authors correlated BCL-2 expression and DNA methylation profiles in human breast cancer and in multiple cell models of acquired endocrine-resistance to determine whether BCL-2 hypermethylation could provide a useful biomarker of response to cytotoxic therapy. [Mol Cancer Ther] Abstract | Press Release

Progesterone Receptor A Stability Is Mediated by GSK-3β Kinase in the Brca1-Deficient Mammary Gland
To further explore how the stability of progesterone receptor is modulated, the authors have found that GSK-3β phosphorylation of progesterone receptor-A (PR-A) facilitates its ubiquitination. Expression of PR-AS390A mutant in the human breast epithelial cells, MCF-10A, results in enhanced proliferation and formation of aberrant acini structure in the 3-D culture. [J Biol Chem] Abstract | Full Article

Regulation of Lipid Synthesis Genes and Milk Fat Production in Human Mammary Epithelial Cell during Secretory Activation
Researchers studied mRNA expression of lipid metabolic enzymes in human mammary epithelial cell in conjunction with the measurement of milk fatty acid composition during secretory activation. [Am J Physiol Endocrinol Metab] Abstract

Platycodin D Inhibits Migration, Invasion, and Growth of MDA-MB-231 Human Breast Cancer Cells via Suppression of Epidermal Growth Factor Receptor-Mediated Akt and MAPK Pathways
Scientists determined the molecular mechanism by which Platycodin D (PD) inhibits the migratory and invasive abilities of the highly metastatic MDA-MB-231 breast cancer cell line. They demonstrated that a non-cytotoxic concentration of PD markedly suppressed wound healing migration, invasion through the matrigel, and adhesion to an extracellular matrix-coated substrate in a dose-dependent manner. [Chem Biol Interact] Abstract

Oncogenic Transformation of Mammary Epithelial Cells by Transforming Growth Factor Beta Independent of Mammary Stem Cell Regulation
Investigators aimed to mimic the transient exposure to transforming growth factor beta (TGFbeta) during involution to determine the persistent effects on premalignant mammary epithelium. CDbetaGeo cells, a transplantable mouse mammary epithelial cell line, were treated in vitro for 14 days with TGFbeta. [Cancer Cell Int] Abstract | Full Article

CLINICAL RESEARCH

Two Years versus One Year of Adjuvant Trastuzumab for HER2-Positive Breast Cancer (HERA): An Open-Label, Randomized Controlled Trial
The authors compared two years of treatment with trastuzumab with one year of treatment, and updated the comparison of one year of trastuzumab versus observation at a median follow-up of eight years, for patients enrolled in the HERceptin Adjuvant (HERA) trial. [Lancet] Abstract

A Phase I Dose-Escalation Study of the VEGFR Inhibitor Tivozanib Hydrochloride with Weekly Paclitaxel in Metastatic Breast Cancer
This phase Ib study investigated the safety/tolerability, pharmacokinetics, and activity of tivozanib with weekly paclitaxel in metastatic breast cancer. Metastatic breast cancer patients with no prior vascular endothelial growth factor receptors (VEGFR) tyrosine kinase inhibitor treatment received daily oral tivozanib (three weeks on, one week off) with weekly paclitaxel 90 mg/m². [Breast Cancer Res Treat] Abstract

Use of Pertuzumab for the Treatment of HER2-Positive Metastatic Breast Cancer
Since resistance to trastuzumab occurs relatively frequently, particularly in the metastatic setting, novel anti-HER2 targeted therapies with complementary and/or synergistic mechanisms of action have been under development. Pertuzumab, a HER2-targeted monoclonal antibody that prevents HER2 dimerization, is the first of a class of promising targeted agents for the treatment of HER2-positive breast cancer. [Adv Ther] Abstract

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Bio-Path Holdings Initiates Development of Liposomal Grb-2 for Triple Negative and Inflammatory Breast Cancers
Bio-Path Holdings, Inc. announced that it is initiating preclinical testing of its lead product candidate, BP-100-1.01 (Liposomal Grb-2), into two additional indications: triple negative breast cancer and inflammatory breast cancer, two cancers characterized by formation of aggressive tumors and relatively high mortality rates. [Bio-Path Holdings, Inc.] Press Release

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Postdoctoral Fellowship – Mechanism of Action of Drugs (Celgene Corporation)

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

Postdoctoral Fellow – Breast Cancer Cell Research (Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Breast Cancer Research (Albert Einstein College of Medicine)

Postdoctoral Fellow – Breast and Renal Cell Carcinoma Research (University of North Carolina – Chapel Hill)

Postdoctoral Position – Breast and Ovarian Cancer Biology (University of Pennsylvania School of Medicine)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

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

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

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