LABORATORY RESEARCH mTOR Signaling Feedback Modulates Mammary Epithelial Differentiation and Restrains Invasion Downstream of PTEN Loss Investigators used isogenic benign mammary organotypic cultures to interrogate the role of mTOR-mediated negative feedback in the specific setting of PTEN inactivation. They found that mTOR signaling promoted basal-like differentiation and repressed nuclear hormone receptor expression after short-term PTEN loss in murine cell cultures analyzed ex vivo. [Cancer Res] Abstract A Leukotriene B4 Receptor-2 Is Associated with Paclitaxel Resistance in MCF-7/DOX Breast Cancer Cells The levels of leukotriene B4 receptor-2 (BLT2) in multidrug-resistant MCF-7/DOX cells were determined using quantitative PCR and FACS analysis. The potential role of BLT2 in the paclitaxel resistance of MCF-7/DOX cells was assessed using a pharmacological inhibitor and small interfering RNA knockdown, and the BLT2-associated resistance mechanism was assessed. [Br J Cancer] Abstract Growth Hormone Potentiates 17β-Estradiol-Dependent Breast Cancer Cell Proliferation Independently of IGF-I Receptor Signaling Researchers examined growth hormone (GH) action in a panel of estrogen receptor positive breast cancer cell lines and found that T47D cells express significant levels of GH receptor and that GH significantly enhances E2-stimulated proliferation in these cells. GH action in T47D cells was independent of changes in insulin-like growth factor-I (IGF-I) and IGF-IR expression and IGF-IR signaling, suggesting that GH can exert direct effects on breast cancer cells. [Endocrinology] Abstract Recombinant GnRH-p53 Protein Sensitizes Breast Cancer Cells to 5-Fluorouracil-Induced Apoptosis In Vitro and In Vivo Researchers constructed a fusion protein consisting of gonadotropin-releasing hormone (GnRH-p53) and p53 moieties. The recombinant protein was directly used to treat human breast cancer cells and athymic nude mice bearing breast cancer xenografts, with or without DNA synthesis-arresting agent 5-fluorouracil. [Apoptosis] Abstract Co-Inhibition of Epidermal Growth Factor Receptor and Insulin-Like Growth Factor Receptor 1 Enhances Radiosensitivity in Human Breast Cancer Cells Scientists investigated the impact of co-inhibition of epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 (IGF-1R) receptor on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression. [BMC Cancer] Abstract | Full Article Hypoxia Stimulates 18F-Fluorodeoxyglucose Uptake in Breast Cancer Cells via Hypoxia Inducible Factor-1 and AMP-Activated Protein Kinase The effect of hypoxia on 18F-fluorodeoxyglucose uptake, and key proteins involved in glucose transport and glycolysis, was studied in MCF7 and MDA231 breast cancer cell lines. [Nucl Med Biol] Abstract Isolation and Characterization of Human Breast Cancer Cells with SOX2 Promoter Activity Researchers developed a reporter system using fluorescent protein driven by the promoter for sex-determining region Y-box 2 (SOX2) gene to detect and isolate living SOX2-positive cells. Results suggested that the cell population with SOX2 promoter activity contains cancer stem cell (CSC)-like cells which show expression profiles different from those of CSC-marker genes previously recognized in human breast cancers. [Biochem Biophys Res Commun] Abstract PLK1 Signaling in Breast Cancer Cells Cooperates with Estrogen Receptor-Dependent Gene Transcription The authors report that PLK1 mediates estrogen receptor (ER)-regulated gene transcription in human breast cancer cells. PLK1 interacts with ER and is recruited to ER cis-elements on chromatin. PLK1-coactivated genes included classical ER target genes such as Ps2, Wisp2, and Serpina3 and were enriched in developmental and tumor-suppressive functions. [Cell Rep] Abstract | Graphical Abstract | Full Article | Press Release CLINICAL RESEARCH Clinical Relevance of Cancer Stem Cells in Bone Marrow of Early Breast Cancer Patients Investigators hypothesized that if cancer stem cells (CSCs) are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients. BM aspirates were collected at the time of surgery from 108 patients with EBC. BM was analyzed for CSCs and aldehyde dehydrogenase activity by flow cytometry. [Ann Oncol] Abstract Cediranib in Combination with Fulvestrant in Hormone-Sensitive Metastatic Breast Cancer: A Randomized Phase II Study Vascular endothelial growth factor (VEGF) may mediate resistance to estrogen receptor (ER) antagonists. Cediranib is a highly potent VEGF signaling inhibitor with activity against all three VEGF receptors. This randomized Phase II study evaluated cediranib plus fulvestrant. The primary endpoint was progression-free survival. [Invest New Drugs] Abstract |