Mammary Cell News Volume 9.41 | Oct 19 2017

TOP STORY

Identification of a Tumor-Promoter Cholesterol Metabolite in Human Breast Cancers Acting through the Glucocorticoid Receptor

Researchers showed that cholesterol epoxide hydrolase metabolizes 5,6-epoxide into cholestane-3β,5α,6β-triol, which is transformed into the oncometabolite 6-oxo-cholestan-3β,5α-diol (OCDO) by 11β-hydroxysteroid-dehydrogenase-type-2. OCDO stimulates breast cancer cell growth by binding to the glucocorticoid receptor, the nuclear receptor of endogenous cortisol. [Proc Natl Acad Sci USA] Abstract

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An Akt3 Splice Variant Lacking the Serine 472 Phosphorylation Site Promotes Apoptosis and Suppresses Mammary Tumorigenesis

Despite being expressed at a substantially lower level than Akt3/+S472 in triple negative breast cancer cells, specific ablation of Akt3/-S472, enhanced, whereas overexpression, suppressed mammary tumor growth-consistent with a significant association with patient survival duration relative to Akt3/+S472. [Cancer Res] Abstract

Sox2 Communicates with Tregs through CCL1 to Promote the Stemness Property of Breast Cancer Cells

Scientists disclose that the primarily cultured Tregs isolated from breast-tumor-bearing Foxp3-EGFP mouse up-regulate the stemness property of breast cancer cells. Tregs increased the side-population and the ALDH^br population of mouse breast cancer cells, promoted their sphere formation in a paracrine manner and enhanced the expression of stemness genes, such as Sox2 etc. [Stem Cells] Abstract

PAK5-Mediated Phosphorylation and Nuclear Translocation of NF-κB-p65 Promotes Breast Cancer Cell Proliferation In Vitro and In Vivo

The authors evaluated p21^cdc42/rac1-activated kinase 5 (PAK5) and p65 staining in breast cancer tissues and paired non-cancerous tissues using tissue microarray technology. The functions of PAK5 were studied in vitro and in vivo. [J Exp Clin Cancer Res] Full Article

Proteomic Profiling of β-hCG Induced Spheres in BRCA1 Defective Triple Negative Breast Cancer Cells

Researchers carried out the total proteomic profiling of HCC1937 β spheres obtained from BRCA1 defective β-hCG expressing stable breast cancer cells to analyze the cell signaling pathways that are active in these cells. [J Proteome Res] Abstract

Mesenchymal Stem Cells from Tumor Microenvironment Favor Breast Cancer Stem Cell Proliferation, Cancerogenic and Metastatic Potential, via Ionotropic Purinergic Signaling

Investigators analyzed the role played by mesenchymal stem cells (MSCs) in breast cancer oncogenesis. Data indicated that interaction of breast cancer cells with MSCs resulted in an increased proliferation and metabolic activity of breast cancer cells, partially due to MSC-derived microvesicles that are shed in the tumor microenvironment. [Sci Rep] Full Article

Regulation of HC11 Mouse Breast Epithelial Cell Differentiation by the E-Cadherin/Rac Axis

To investigate the functional relationship between the transforming ability of Rac and its role as an integral component of the differentiative E-cadherin signaling pathway, they introduced a mutationally activated form of Rac, Rac^V12, into the mouse breast epithelium-derived cell line, HC11. [Exp Cell Res] Abstract

STAT3 but Not HIF-1α Is Important in Mediating Hypoxia-Induced Chemoresistance in MDA-MB-231, a Triple Negative Breast Cancer Cell Line

The effect of hypoxia on the sensitivity of MDA-MB-231 cells to cisplatin and their stem-like features was evaluated and the role of hypoxia inducible factor-1α (HIF-1α) in both phenomena was assessed. Scientists showed that hypoxia significantly increased MDA-MB-231 resistance to cisplatin. [Cancers (Basel)] Full Article

5,6,7,3′,4′,5′-Hexamethoxyflavone Inhibits Growth of Triple-Negative Breast Cancer Cells via Suppression of MAPK and Akt Signaling Pathways and Arresting Cell Cycle

The anticancer activity of the well-known nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone) was compared against its less studied structural isomer 5,6,7,3′,4′,5′-hexamethoxyflavone. [Int J Oncol] Abstract

Anticancer Activity of VmCT1 Analogs against MCF-7 Cells

Some cationic antimicrobial peptides exhibit anticancer activity so Phe-Leu-Gly-Ala-Leu-Trp-Asn-Val-Ala-Lys-Ser-Val-Phe-NH₂ (VmCT1) analogs were tested in order to verify the anticancer activity of this family of peptides. The analogs were synthesized, purified, characterized and the conformational studies were performed. The anticancer activity was assessed against MCF-7 mammary cancer cells. [Chem Biol Drug Des] Abstract

CDK4/6 Blockade in Breast Cancer: Current Experience and Future Perspectives

The authors illustrate how CDK4/6-selective inhibitors got approval for the treatment of patients with either newly diagnosed or pretreated advanced hormone receptor positive, HER2-negative breast cancer. Data about potential predictive biomarkers, as well as preclinical and preliminary clinical evidence for potential antitumor activity of CDK4/6 inhibition in other breast cancer subtypes is provided. [Expert Opin Investig Drugs] Abstract

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Eos Biosciences Announces Issuance of Additional U.S. Patent For Targeted Breast Cancer Therapy

Eos Biosciences, Inc. announced that the U.S. Patent and Trademark Office has now issued Eos Biosciences a second patent for Eos-001, the company’s HER3-targeted Eosome with doxorubicin payload. Eos-001 is a proof-of-concept proprietary product in preclinical development, intended to address Triple Negative Breast Cancer and HER2⁺ breast cancer resistant or nonresponsive to first line therapies. [Eos Biosciences, Inc.] Press Release

US FDA Accepts Regulatory Submission for Lynparza in Metastatic Breast Cancer and Grants Priority Review

AstraZeneca and Merck & Co., Inc., announced that the FDA has accepted and granted Priority Review for a supplemental New Drug Application for the use of Lynparza tablets in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic settings. [AstraZeneca] Press Release

Efforts to Save Leading Hungarian University Hit Hurdle

The threatened Central European University in Budapest has been dealt a blow in its efforts to avert possible closure in Hungary. The country’s parliament voted to postpone, for a year, a decision that would allow the university to keep operating there. [Nature News] Editorial

New Definitions of Scientific Units Are on the Horizon

Revamped definitions of scientific units are on their way. In the biggest overhaul of the international system of units since its inception in 1960, a committee is set to redefine four basic units — the ampere, the kilogram, the kelvin and the mole — using relationships to fundamental constants, rather than abstract or arbitrary definitions. [Nature News] Editorial

Top Chinese University to Consider Social-Media Posts in Researcher Evaluations

One of China’s most prestigious universities plans to give some articles in newspapers and posts on major social-media outlets the same weight as peer-reviewed publications when it evaluates researchers. [Nature News] Editorial

Rand Paul Takes a Poke at U.S. Peer Review Panels

Senate Republicans have launched a new attack on peer review by proposing changes to how the U.S. government funds basic research. [ScienceInsider] Editorial

NEW 10^th Annual European Network of Breast Development and Cancer (ENBDC) Workshop: Methods in Mammary Gland Biology and Breast Cancer
March 15-17, 2018
Weggis, Switzerland

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NEW Physician Scientist – Translational Research in Breast Cancers (University of New Mexico)

NEW Postdoctoral Fellow – Translational Research in Breast Cancer (University of Texas Southwestern Medical Center)

Postdoctoral Training Fellows – Breast Cancer Research (Institute of Cancer Research)

Postdoctoral Positions – Interdisciplinary Translational Research (University of Texas Health Science Center at San Antonio)

Postdoctoral Fellowship – Breast Cancer Research (Geisel School of Medicine at Dartmouth)

Assistant Professor – Cancer Biology (Perelman School of Medicine)

Assistant Professor – Cancer Research (University of Minnesota)

Postdoctoral Position – Cancer Metabolism (University of Louvain)

Postdoctoral Position – Transcriptomics and Cancer Epigenetics (Universität Basel)

Postdoctoral Opportunities – Cancer Research (Albert Einstein College of Medicine in New York)

Faculty Positions – Basic and Translational Cancer Research (Texas Tech University Health Science Center El Paso)

Associate Medical Director/Medical Director – Breast Cancer (Genentech, Inc.)

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