Volume 5.24 | Jun 20

Mammary Cell News 5.24 June 20, 2013
Mammary Cell News
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TOP STORY
Par-4 Downregulation Promotes Breast Cancer Recurrence by Preventing Multinucleation following Targeted Therapy
Scientists report that Par-4 is downregulated during tumor recurrence and that Par-4 downregulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. [Cancer Cell] Abstract | Press Release

Learn More: Column-Free Enrichment of Mouse Mammary Stem & Progenitor Cells
PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

Molecular Profiling of Human Mammary Gland Links Breast Cancer Risk to a p27+ Cell Population with Progenitor Characteristics
Researchers characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. They found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. [Cell Stem Cell]
Abstract | Graphical Abstract

Selective Estrogen Receptor Modulators and Pharmacogenomic Variation in ZNF423 Regulation of BRCA1 Expression: Individualized Breast Cancer Prevention 
An initial discovery genome-wide association study identified common single-nucleotide polymorphisms (SNP) in or near the ZNF423 and CTSO genes that were associated with breast cancer risk during selective estrogen receptor modulators therapy. The authors then showed that both ZNF423 and CTSO participated in the estrogen-dependent induction of BRCA1 expression, in both cases with SNP-dependent variation in induction. [Cancer Discov]
Abstract | Press Release

CD73 Promotes Anthracycline Resistance and Poor Prognosis in Triple Negative Breast Cancer
Using mouse models of breast cancer, scientists demonstrated that CD73 overexpression in tumor cells conferred chemoresistance to doxorubicin, a commonly used anthracycline, by suppressing adaptive antitumor immune responses via activation of A2A adenosine receptors. [Proc Natl Acad Sci USA] Abstract

Antioxidant Enzymes Mediate Survival of Breast Cancer Cells Deprived of Extracellular Matrix
Investigators report the discovery of a prominent role for antioxidant enzymes, including catalase and superoxide dismutase, in facilitating the survival of breast cancer cells after extracellular matrix (ECM)-detachment. Enhanced expression of antioxidant enzymes in nonmalignant mammary epithelial cells detached from ECM resulted in ATP elevation and survival in the luminal space of mammary acini. [Cancer Res]
Abstract

The Gene Desert Mammary Carcinoma Susceptibility Locus Mcs1a Regulates Nr2f1 Modifying Mammary Epithelial Cell Differentiation and Proliferation
Researchers developed a megadeletion mouse model, which lacks 535 Kb of sequence containing the Mcs1a ortholog. Global gene expression analysis by RNA-seq revealed that in the mouse mammary gland, the orphan nuclear receptor gene Nr2f1/Coup-tf1 is regulated by Mcs1a. In resistant Mcs1a congenic rats, as compared with susceptible congenic control rats, they found Nr2f1 transcript levels to be elevated in mammary gland, epithelial cells, and carcinoma samples. [PLoS Genet] Full Article

The Pluripotency Factor Nanog Promotes Breast Cancer Tumorigenesis and Metastasis
To elucidate the physiological roles of Nanog in tumorigenesis, the authors developed an inducible Nanog transgenic mouse model, in which the expression of Nanog in adult tissues can be induced via LoxP/Cre-mediated deletion. Their findings indicate that overexpression of Nanog in the mammary gland is not sufficient to induce mammary tumor. However, when coexpressed with Wnt-1 in the mouse mammary gland, it promotes mammary tumorigenesis and metastasis. [Oncogene] Abstract

Apoptotic Circulating Tumor Cells (CTCs) in Early and Metastatic Breast Cancer Patients
Since it is unclear if all CTCs are capable of generating metastasis, scientists investigated apoptotic and proliferative status in 56 CTC-positive breast cancer patients. Double staining immunofluorescence experiments were performed in peripheral blood mononuclear cells cytospins using the pancytokeratin A45-B/B3 antibody and either M30 or Ki67 antibodies. [Mol Cancer Ther] Abstract

miR-181a Enhances Drug Sensitivity in Mitoxantone-Resistant Breast Cancer Cells by Targeting Breast Cancer Resistance Protein (BCRP/ABCG2)
The authors investigated the role of microRNAs (miRNAs) in regulation of BCRP expression and BCRP-mediated drug resistance in breast cancer cells. Microarray analysis was performed to determine the differential expression patterns of miRNAs that target BCRP between the MX-resistant breast cancer cell line MCF-7/MX and its parental MX-sensitive cell line MCF-7. [Breast Cancer Res Treat] Abstract

CLINICAL RESEARCH

Six Months versus 12 Months of Adjuvant Trastuzumab for Patients with HER2-Positive Early Breast Cancer (PHARE): A Randomized Phase III Trial
Investigators did an open-label, randomized, phase III trial in 156 centers in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to six months of trastuzumab before randomization were eligible. [Lancet Oncol] Abstract

Capecitabine Plus Paclitaxel versus Epirubicin Plus Paclitaxel as First-Line Treatment for Metastatic Breast Cancer: Efficacy and Safety Results of a Randomized, Phase III Trial by the AGO Breast Cancer Study Group
Researchers conducted a randomized, phase III, noninferiority trial comparing capecitabine plus paclitaxel with epirubicin plus paclitaxel as first-line therapy for metastatic breast cancer, regarding progression-free survival as primary efficacy endpoint. [Breast Cancer Res Treat] Abstract

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SCIENCE NEWS
Osteoporosis Drug Stops Growth of Breast Cancer Cells, Even in Resistant Tumors
A drug approved in Europe to treat osteoporosis has now been shown to stop the growth of breast cancer cells, even in cancers that have become resistant to current targeted therapies, according to a Duke Cancer Institute study. The findings indicate that the drug bazedoxifene packs a powerful one-two punch that not only prevents estrogen from fueling breast cancer cell growth, but also flags the estrogen receptor for destruction. [Press release from Duke University Health System discussing research presented at ENDO 2013 – The Endocrine Society’s 95th Annual Meeting, San Francisco] Press Release

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INDUSTRY NEWS

EORTC Study Opens for Elderly Patients with HER-2 Positive Metastatic Breast Cancer
The main objectives of EORTC trial 75111 – 10114 are to evaluate the efficacy as measured by progression free survival at six months following treatment with pertuzumab combined with trastuzumab or pertuzumab combined with trastuzumab plus metronomic chemotherapy in elderly metastatic breast cancer patients and to select attractive treatments for further development in Phase III. [EurekAlert!] Press Release

GeneDx to Launch Comprehensive Breast Cancer Genetic Test

GeneDx announced its intention to launch a suite of comprehensive genetic tests for inherited cancers including BRCA1 and BRCA2 genes, given the Supreme Court’s ruling in the Association for Molecular Pathology vs. Myriad Genetics case. GeneDx will now bring its expertise and reputation for service to inherited cancers and will offer a 27-gene panel for breast and ovarian cancers. [GeneDx] Press Release


Nuclea Biotechnologies and SUNY’s NanoCollege Announce $1 Million Partnership to Advance Nanotechnology-Enabled Cancer Research
Underscoring the strategic blueprint of Governor Andrew M. Cuomo in fueling New York’s growing reputation as a hub for nanotechnology-enabled innovation, SUNY’s College of Nanoscale Science and Engineering and Pittsfield, Massachusetts-based Nuclea Biotechnologies, Inc. announced the launch of a $1 million research partnership to enable the development and commercialization of a high-throughput nanochip to accelerate the diagnosis and treatment of breast, colon, prostate and other cancers. [Nuclea Biotechnologies, Inc.] 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 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
October 19-23, 2013
Boston, United States

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

JOB OPPORTUNITIES

NEW Postdoctoral Fellow – Breast and Renal Cell Carcinoma Research (University of North Carolina – Chapel Hill)

Postdoctoral Position – lncRNA and RNA Binding Protein Interaction in Mammary Cancer Stem Cell (CIBIO, University of Trento)

PhD Studentship – Breast Cancer Biology (Royal College of Surgeons in Ireland)

Postdoctoral Position – Breast and Ovarian Cancer Biology (University of Pennsylvania School of Medicine)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Position – Breast Cancer/Stem Cell Biology (UC College of Medicine)

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


Postdoctoral Fellow – Cancer Genes in Breast Cancer (MD Anderson Cancer Center)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)


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