Volume 5.13 | Apr 4

Mammary Cell News 5.13 April 4, 2013
Mammary Cell News
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TOP STORY
Genome-Wide Reprogramming of the Chromatin Landscape Underlies Endocrine Therapy Resistance in Breast Cancer
Scientists demonstrated that genome-wide reprogramming of the chromatin landscape, defined by epigenomic maps for regulatory elements or transcriptional activation and chromatin openness, underlies resistance to endocrine therapy. This annotation reveals endocrine therapy-response specific regulatory networks where the NOTCH pathway is overactivated in resistant breast cancer cells, whereas classical estrogen receptor alpha signaling is epigenetically disengaged. [Proc Natl Acad Sci USA] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

Elevated snoRNA Biogenesis Is Essential in Breast Cancer
Researchers report that small nucleolar RNAs (snoRNAs) and fibrillarin are frequently overexpressed in both murine and human breast cancer as well as in prostate cancers, and significantly, that this overexpression is essential for tumorigenicity in vitro and in vivo. [Oncogene] Abstract

GSK-3β Signaling Determines Autophagy Activation in the Breast Tumor Cell Line MCF7 and Inclusion Formation in the Non-Tumor Cell Line MCF10A in Response to Proteasome Inhibition
Proteasome inhibitors are used for the treatment of some types of cancer, whereas autophagy seems to have a dual role in tumor cell survival and death. However, the relationship between both pathways has not been extensively studied in tumor cells. Researchers investigated both proteolytic systems in the human epithelial breast non-tumor cell line MCF10A and in the human epithelial breast tumor cell line MCF7. [Cell Death Dis] Abstract

Estrogen Receptor-α Variant, ER-α36, Is Involved in Tamoxifen Resistance and Estrogen Hypersensitivity
Researchers investigated the function and underlying mechanism of ER-α36 in tamoxifen resistance. They found that tamoxifen increased ER-α36 concentrations and tamoxifen-resistant MCF7 cells expressed high concentrations of ER-α36. In addition, MCF7 cells with forced expression of recombinant ER-α36 and H3396 cells expressing high concentrations of endogenous ER-α36 were resistant to tamoxifen. [Endocrinology] Abstract

7β-Estradiol Activates Glucose Uptake via GLUT4 Translocation and PI3K/Akt Signaling Pathway in MCF-7 Cells
Researchers tested the rapid effects of 17β-estradiol or its membrane-impermeable form conjugated with bovine serum albumin on glucose uptake in a positive estrogen receptor breast cancer cell line, through the possible relationship between key components of the PI3K/Akt signaling pathway and acute steroid treatment. [Endocrinology] Abstract

The Wnt Signaling Pathway Is Upregulated in an In Vitro Model of Acquired Tamoxifen Resistant Breast Cancer
An in vitro model of acquired Tamoxifen resistance was generated by growing the estrogen receptor alpha positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen. Alterations in the Wnt signaling pathway and epithelial to mesenchymal transition in response to Tamoxifen and treatment with the Wnt inhibitor, IWP-2 were measured via quantitative RT-PCR and TOP/FOP Wnt reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were determined by MTT proliferation assays. [BMC Cancer] Abstract | Full Article

Knockdown of HMGA1 Inhibits Human Breast Cancer Cell Growth and Metastasis in Immunodeficient Mice
Researchers silenced HMGA1 expression in the human breast cancer cell line MDA-MB-231 using an RNA interference vector, and observed a significant reduction in anchorage-independent growth and tumorsphere formation, which respectively indicate loss of tumorigenesis and self-renewal ability. Moreover, silencing HMGA1 significantly impaired xenograft growth in immunodeficient mice, and while control cells metastasized extensively to the lungs and lymph nodes, HMGA1-silenced cells generated only a few small metastases. [Biochem Biophys Res Commun] Abstract

The Effect of Estrogen on Prolidase-Dependent Regulation of HIF-1α Expression in Breast Cancer Cells
The role of estrogen in breast cancer progression and activation of prolidase activity and HIF-1α led the authors to study the effect of estrogen on nuclear HIF-1α expression in breast cancer estrogen-dependent MCF-7 and estrogen-independent MDA-MB-231 cells. They found that in MCF-7 cells (expressing α and β estrogen receptor) cultured without estrogen receptor activator (phenol red, estradiol), HIF-1α was down-regulated, compared to the cells cultured with estrogen receptor activator. [Mol Cell Biochem] Full Article


CLINICAL RESEARCH


Identification of Prognosis-Relevant Subgroups in Patients with Chemoresistant Triple Negative Breast Cancer
Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. Researchers developed a clinically relevant signature for patients with chemoresistant TNBC. [Clin Cancer Res] Abstract

Phosphorylation of AKT Pathway Proteins Is Not Predictive of Benefit of Taxane Therapy in Early Breast Cancer
Pre-clinical data support a link between PI3 K/AKT signaling and taxane resistance. Using the UK taxotere as adjuvant chemotherapy trial, researchers tested the hypothesis that activation of AKT or downstream markers, p70S6K or p90RSK, identifies patients with reduced benefit from taxane chemotherapy. [Breast Cancer Res Treat] Abstract

Discrepancy between Routine and Expert Pathologists’ Assessment of Non-Palpable Breast Cancer and Its Impact on Locoregional and Systemic Treatment
The authors assessed the impact of inter-observer variability on treatment strategy in patients operated for clinically node negative, non-palpable breast carcinomas. In the context of a multicenter randomized controlled trial, clinical and histological data of 310 patients with clinically node negative non-palpable invasive breast cancer were prospectively collected. Histological assessment of the primary tumor and sentinel nodes was first performed in a routine setting, subsequently central review took place. [Eur J Pharmacol] Full Article

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REVIEWS

Signaling Cross-Talk in the Resistance to HER Family Receptor Targeted Therapy
Extensive studies from both clinical and laboratory research have identified several molecular mechanisms underlying intrinsic and acquired drug resistance. Among them is the role of signaling cross-talk between the epidermal growth factor receptor (EFGR)/human EGFR 2 (HER2) and other signaling pathways. In this review, the authors focus particularly on this signaling cross-talk at the receptor, mediator and effector levels, and further discuss alternative approaches to overcome resistance. [Oncogene] Abstract

The Hedgehog Signaling Pathway in Breast Development, Carcinogenesis and Cancer Therapy
The authors provide a comprehensive overview of the canonical Hedgehog signaling pathway in mammals, highlight its roles in mammary gland development and breast carcinogenesis and discuss its potential therapeutic value in the basal-like subtype of breast cancer. [Breast Cancer Res]
Abstract

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INDUSTRY NEWS

DR Systems’ Certified Cloud-Based eHR System Enabled Breast Center of Acadiana to Successfully Attest to Meaningful Use
DR Systems announced that its customer Breast Center of Acadiana, in Louisiana, received its federal incentive funds for successfully completing the Meaningful Use Stage 1 attestation. Breast Center of Acadiana implemented DR Systems’ cloud-based eHR for Meaningful Use in August of 2012 and started meaningfully collecting data from October 1 to December 31, 2012. [DR Systems, Inc.] Press Release

NewLink Genetics Initiates Phase II Trial of IDO Pathway Inhibitor, Indoximod, for the Treatment of Metastatic Breast Cancer
NewLink Genetics Corporation announced the initiation of a double-blind, randomized, placebo-controlled Phase II clinical study of its first IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor, indoximod, in patients with metastatic breast cancer. [NewLink Genetics Corporation] Press Release

QVC and Fashion Footwear Association of New York Invest in Personalized Breast Cancer Therapy Research
QVC and the Fashion Footwear Association of New York, building on a 19 year philanthropic relationship supporting breast cancer research, have announced a $140,000 grant to fund research at The Wistar Institute on a specific and deadly form of breast cancer called triple negative. [PR Newswire Association LLC]
Press Release

POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS
NEW Fourth International Breast Cancer Prevention Symposium: Genes, the Environment and Breast Cancer Risk
October 11-13, 2013
Beirut, Lebanon


Visit our events page to see a complete list of events in the mammary cell community.
JOB OPPORTUNITIES

Postdoctoral Position – Establishing the Role of Key Recurring Genetic Mutations in Endocrine Resistant Breast Cancer (AstraZeneca)

PhD Studentship – Signal Transduction and Cancer Research (McGill University)

Postdoctoral Position – Breast Cancer Research (Albert Einstein College Medicine)

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

Postdoctoral Position – Hypoxia Signaling, Prolyl Hydroxylases and Cancer (UNC-Chapel Hill)

Postdoctoral Position – Breast Cancer (UT Southwestern Medical Center at Dallas)

Product Director – Breast Marketing (Genomic Health)


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