Mammary Cell News Volume 11.36 | Sep 19 2019

TOP STORY

Deubiquitylation and Stabilization of Notch1 Intracellular Domain by Ubiquitin-Specific Protease 8 Enhance Tumorigenesis in Breast Cancer

Ubiquitin-specific protease 8 (USP8) specifically stabilized and deubiquitylates Notch1 intracellular domain (NICD) through a direct interaction. The inhibition of USP8 downregulated the Notch signalling pathway via NICD destabilization, resulting in the retardation of cellular growth, wound closure, and colony forming ability of breast cancer cell lines. [Cell Death Differ] Abstract

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Epigenetic Re-Wiring of Breast Cancer by Pharmacological Targeting of C-Terminal Binding Protein

Micromolar concentrations of C-terminal binding protein (CtBP) inhibitors produced significant de-repression of epigenetically silenced pro-epithelial genes, preferentially in the triple-negative breast cancer cell line MDA-MB-231. This epigenetic reprogramming occurred through eviction of CtBP from gene promoters; disrupted recruitment of chromatin-modifying protein complexes containing LSD1, and HDAC1; and re-wiring of activating histone marks at targeted genes. [Cell Death Dis] Full Article

Subtype-Specific Transcriptional Regulators in Breast Tumors Subjected to Genetic and Epigenetic Alterations

Scientists used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis they observed that these subtypes were determined by a distinct repertoire of lineage-specific transcription factors. [Bioinformatics] Full Article

Clinical Implications of Drug-Screening Assay for Recurrent Metastatic Hormone Receptor-Positive, Human Epidermal Receptor 2-Negative Breast Cancer Using Conditionally Reprogrammed Cells

Researchers elucidated the clinical relevance of cultured cells derived from patients with recurrent hormone receptor-positive⁺/human epidermal receptor 2-negative^– metastatic breast cancer. The recently established conditionally reprogrammed cell system enabled them to examine heterogeneity, drug sensitivity and cell function using patient-derived tumor samples. [Sci Rep] Full Article

Anti-Tumor Activity of BET Inhibitors in Androgen-Receptor-Expressing Triple-Negative Breast Cancer

Investigators demonstrated potent anti-tumor effects of the bromodomain extra-terminal motif (BET) inhibitor JQ1 against androgen receptor-positive triple-negative breast cancer cell lines using cell viability and cell cycle analysis. To reveal the mechanisms of JQ1 effects, multiplex gene expression analysis and immunoblotting assays were used. [Sci Rep] Full Article

Development of a ZHER3-Affibody-Targeted Nano-Vector for Gene Delivery to HER3-Overexpressed Breast Cancer Cells

An affibody molecule against human epidermal growth factor receptor-3 (HER3) was conjugated to a biomimetic peptide RALA and the ability of the fusion vector for targeting HER3 and afterward delivering specific genes in breast cancer cells was evaluated. The results demonstrated that the biopolymeric platform, which contained an affibody-conjugated RALA peptide, could effectively condense DNA into nanoparticles and target the overexpressed HER3 receptors in breast cancer cells and transfer specific genes. [Macromol Biosci] Abstract

The Milk Protein Alpha-Casein Suppresses Triple Negative Breast Cancer Stem Cell Activity via STAT and HIF-1alpha Signalling Pathways in Breast Cancer Cells and Fibroblasts

Researchers examined the effects of the milk protein alpha-casein over-expression in the triple negative MDA-MB-231 breast cancer cell line. The effects of recombinant alpha-casein added exogenously to MDA-MB-231 breast cancer cells, and immortalised human fibroblasts were also investigated. [J Mammary Gland Biol Neoplasia] Full Article

A MiR-21-3p Centric Regulatory Network in Dairy Cow Mammary Epithelial Cells Proliferation

The function of miR-21-3p on bovine mammary gland epithelial cells was detected by MTT assay and flow cytometry analysis, which showed that miR-21-3p significantly promoted the cell viability and proliferation. Then the regulating mechanism of miR-21-3p on cell viability and proliferation was elucidated. [J Agric Food Chem] Abstract

2-Deoxyglucose and Newcastle Disease Virus Synergize to Kill Breast Cancer Cells by Inhibition of Glycolysis Pathway through Glyceraldehyde3-Phosphate Downregulation

The authors used the glucose analog 2-deoxyglucose (2-DG) as a competitor molecule of glucose. To further enhance the effectiveness of 2-DG, the Newcastle disease virus (NDV) was used as a combination virotherapy to enhance the anti-tumor effect. Human and mouse-breast cancer cells were treated by NDV and/or 2-DG. [Front Biosci] Abstract

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Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer

The authors summarize the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices. They present the data on anti-HER2 clinical research of neoadjuvant, adjuvant, and metastatic studies from the past two decades. [Signal Transduct Target Ther] Abstract

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Roche’s Fixed-Dose Subcutaneous Combination of Perjeta and Herceptin Showed Non-Inferiority When Compared to Intravenous Formulations for People with HER2-Positive Breast Cancer

Roche announced the Phase III FeDeriCa study met its primary endpoint. The study showed that a new investigational fixed-dose combination of Perjeta^® and Herceptin^®, administered by subcutaneous injection in combination with intravenous chemotherapy, demonstrated non-inferior levels of Perjeta in the blood compared to standard IV infusion of Perjeta plus Herceptin and chemotherapy in people with HER2-positive early breast cancer. [Roche] Press Release

Generex Biotechnology Announces First Patient Enrolled in the Phase II Clinical Trial of AE37 in Combination with Pembrolizumab (Keytruda^®) for the Treatment of Triple Negative Breast Cancer

Generex Biotechnology Corporation announced that the NSABP Foundation, Inc. has enrolled the first patient in the study: A Phase II Clinical Trial of Pembrolizumab in combination with the AE37 Peptide Vaccine in Patients with metastatic triple negative breast cancer. [Generex Biotechnology Corporation] Press Release

New Journal Seeks Typically Overlooked Studies

On September 18, Cambridge University Press launched an open-access journal that will address issues in research by taking a different approach to publishing. The journal, Experimental Results, will include findings that have inconclusive or negative results and articles that reproduce or dispute existing research. [The Scientist] Editorial

US Awards $3 Million to Fill Gaps in Medical Marijuana Research

The US government will spend $3 million to find out if marijuana can relieve pain, but none of the money will be used to study the part of the plant that gets people high. Nine research grants announced are for work on CBD, the trendy ingredient showing up in cosmetics and foods, and hundreds of less familiar chemicals. THC research was excluded. [STAT News] Editorial

NEW AACR International Conference on Molecular Targets and Cancer Therapeutics
October 26-30, 2019
Boston, Massachusetts, United States

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NEW Research Scientist – Breast Cancer (The University of Pittsburgh)

Postdoctoral Researcher – Nanomedicine and Immunoengineering (University of California San Diego)

Postdoctoral Research Fellow – Epithelial Growth in Development and Cancer (Fred Hutchinson Cancer Research Center)

Project Scientist – Breast and Hematological Tumors (Cedars-Sinai)

Postdoctoral Research Scientist – Role of Cancer-Associated Fibroblast Metabolism in Breast Cancer (Cancer Research UK Beatson Institute)

Postdoctoral Fellow – Breast and Prostate Cancer (Mayo Clinic Comprehensive Cancer Center)

Research Assistant – Endocrinology in Breast Cancer and Diabetes (Northwell Health)

Bioinformatician – Breast Cancer (Royal College of Surgeons in Ireland)

Postdoctoral Fellow – T-Cell Immunotherapy in Cancers (Memorial Sloan Kettering Cancer Center)

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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