LABORATORY RESEARCH Combined Targeting of HER2 and VEGFR2 for Effective Treatment of HER2-Amplified Breast Cancer Brain Metastases Researchers developed a mouse model of Human Epidermal Growth Factor Receptor 2 (HER2)-amplified breast cancer brain metastasis using an orthotopic xenograft of BT474 cells. As seen in patients, the HER2 inhibitors trastuzumab and lapatinib controlled tumor progression in the breast but failed to contain tumor growth in the brain. [Proc Natl Acad Sci USA] Full Article Epithelial-to-Mesenchymal Transition Induced by TGF-β1 Is Mediated by Blimp-1-Dependent Repression of BMP-5 TGF-β1 treatment of untransformed NMuMG mammary epithelial and MDA-MB-231 breast cancer cells was shown to induce Blimp-1 expression, which promoted an epithelial-to-mesenchymal transition signature and cell migration. [Cancer Res] Abstract The Milk Protein α-Casein Functions as a Tumor Suppressor via Activation of STAT1 Signaling, Effectively Preventing Breast Cancer Tumor Growth and Metastasis Scientists identified the milk protein α-casein as a novel suppressor of tumor growth and metastasis. Met-1 mammary tumor cells expressing α-casein showed a ~5-fold reduction in tumor growth and a near 10-fold decrease in experimental metastasis. [Cell Cycle] Abstract Estrogen Receptor α Signaling Regulates Breast Tumor-Initiating Cells by Downregulating miR-140 which Targets the Transcription Factor SOX2 The authors found that the stem cell self-renewal regulator SOX2 is a novel target of microRNA-140 (miR-140), and that this miR-140/SOX2 pathway critically regulates breast tumor initiating cell survival, providing a new link between estrogen receptor α signaling and breast cancer stem cell maintenance.[J Biol Chem] Full Article Endocrine Disruptors Fludioxonil and Fenhexamid Stimulate miR-21 Expression in Breast Cancer Cells Investigators examined the effect of Fenhexamid and Fludioxonil on the expression of the oncomiR miR-21 in MCF-7, T47D, and MDA-MB-231 human breast cancer cells and downstream targets of miR-21 in MCF-7 cells. [Toxicol Sci] Abstract Surveillance of Spontaneous Breast Cancer Metastasis by TRAIL-Expressing CD34+ Cells in a Xenograft Model Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), delivered as a membrane-bound molecule expressed on the surface of adenovirus-transduced CD34+ cells, was analyzed for its apoptotic activity in vitro on 12 breast cancer cell lines representing estrogen receptor-positive, HER2+ and triple-negative (TN) subtypes and for its effect on tumor growth, vascularization, necrosis, and lung metastasis incidence in NOD/SCID mice xenografted with the TN breast cancer line MDA-MB-231. [Breast Cancer Res Treat] Full Article Eliminating Drug Resistant Breast Cancer Stem-Like Cells with Combination of Simvastatin and Gamma-Tocotrienol Researchers showed that drug resistant human breast cancer cells are enriched in cancer stem-like cells (CSCs) and express elevated levels of Stat-3 signaling mediators, which contribute to CSC enrichment. Simvastatin and gamma-tocotrienol eliminated enriched CSCs and suppress expression of Stat-3 signaling mediators via inhibition of the mevalonate pathway and activation of de novo ceramide synthesis pathway, respectively. [Cancer Lett] Abstract Effects of the Missense Mutations in Canine BRCA2 on BRC Repeat 3 Functions and Comparative Analyses between Canine and Human BRC Repeat 3 Scientists focused on two previously reported canine BRCA2 mutations (T1425P and K1435R) in BRC repeat 3 (BRC3), derived from mammary tumor samples. These mutations affected the interaction of canine BRC3 with RAD51, and were considered deleterious. [PLoS One] Full Article Pleiotrophin Expression and Function in the Mouse Mammary Gland and Mammary Epithelial Cells Scientists examined the expression of Pleiotrophin and its receptor Anaplastic Lymphoma Kinase at various stages of mouse mammary gland development and found that their expression in epithelial cells is regulated in parallel during pregnancy. [PLoS One] Full Article CLINICAL RESEARCH DNA Methylation Profiling in Breast Cancer Discordant Identical Twins Identifies DOK7 as Novel Epigenetic Biomarker Using whole blood from 15 twin pairs discordant for breast cancer and high-resolution (450k) DNA methylation analysis researchers identified 403 differentially methylated CpG sites including known and novel potential breast cancer genes. [Carcinogenesis] Full Article | Press Release Non-Sentinel Lymph Node Metastasis Prediction in Breast Cancer with Metastatic Sentinel Lymph Node: Impact of Molecular Subtypes Classification To decipher the interaction between the molecular subtype classification and the probability of a non-sentinel node metastasis in breast cancer patients with a metastatic sentinel lymph-node, researchers applied two validated predictors on two large independent datasets. [PLoS One] Full Article |