Volume 5.27 | Jul 11

Mammary Cell News 5.27 July 11, 2013
Mammary Cell News
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Targeting BCL-2 with the BH3 Mimetic ABT-199 in Estrogen Receptor-Positive Breast Cancer
Researchers generated estrogen receptor-positive primary breast tumor xenografts that recapitulate the primary tumors and demonstrated that the BH3 mimetic ABT-737 markedly improves tumor response to the antiestrogen tamoxifen. Despite abundant BCL-XL expression, similar efficacy was observed with the BCL-2 selective inhibitor ABT-199, revealing that BCL-2 is a crucial target. [Cancer Cell]
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Learn More: Column-Free Enrichment of Mouse Mammary Stem & Progenitor Cells
PUBLICATIONS (Ranked by impact factor of the journal)

ANTXR1, A Stem Cell Enriched Functional Biomarker, Connects Collagen Signaling to Cancer Stem-Like Cells and Metastasis in Breast Cancer
The anthrax toxin receptor ANTXR1 has been identified as a functional biomarker of normal stem cells and breast cancer stem-like cells. Primary stem cell-enriched basal cells (CD49f+/EpCAM-/Lin-) expressed higher levels of ANTXR1 compared to mature luminal cells. CD49f+/EpCAM-, CD44+/EpCAM-, CD44+/CD24- or ALDEFLUOR-positive subpopulations of breast cancer cells were enriched for ANTXR1 expression. [Cancer Res] Abstract

Distinct FAK Activities Determine Progenitor and Mammary Stem Cell Characteristics
Researchers showed that conditional deletion of focal adhesion kinase (FAK) in embryonic mammary epithelial cells decreases luminal progenitors and basal mammary stem cells, reducing their colony-forming and regenerative potentials in a cell autonomous manner. [Cancer Res] Abstract

Insulin Receptor Phosphorylation by Endogenous Insulin or the Insulin Analog AspB10 Promotes Mammary Tumor Growth Independent of the IGF-1 Receptor
Scientists hypothesized that endogenous hyperinsulinemia increases mammary tumor growth by directly activating the insulin receptor (IR) rather than the insulin-like growth factor-1 receptor (IGF-1R) or hybrid receptors. They aimed to determine whether stimulating the IR with the insulin analog AspB10 could increase tumor growth independent of IGF-1R signaling. [Diabetes] Abstract

Regulation of Cell Proliferation and Migration by Keratin19-Induced Nuclear Import of Early Growth Response-1 in Breast Cancer Cells
The authors investigated the functional analysis of keratin19 (KRT19) in human breast cancer. Using a shRNA system, they silenced KRT19 in breast cancer cells. KRT19 silencing was verified by western blot analysis and immunocytochemistry. They further examined the effect of KRT19 silencing on breast cancer cells by cell proliferation, migration, invasion, colony formation assay, cell cycle analysis, immunocytochemistry, immunohistochemistry and mouse xenograft assay. [Clin Cancer Res] Abstract

MicroRNA-19a-3p Inhibits Breast Cancer Progression and Metastasis by Inducing Macrophage Polarization through Downregulated Expression of Fra-1 Proto-Oncogene
Investigators demonstrated that microRNA-19a-3p, broadly conserved among vertebrates, was downregulated in RAW264.7 macrophage cells of the M2 phenotype in conditoned medium of 4T1 mouse breast tumor cells. This downregulation correlated with an increased expression of the Fra-1 gene, which was reported to act as a pro-oncogene by supporting the invasion and progression of breast tumors. [Oncogene] Abstract

Identification of p130Cas/ErbB2-Dependent Invasive Signatures in Transformed Mammary Epithelial Cells
By comparing coding and non-coding gene expression profiles, the authors defined the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. [Cell Cycle] Abstract

Bone Morphogenetic Proteins Stimulate Mammary Fibroblasts to Promote Mammary Carcinoma Cell Invasion
Researchers sought to determine the effect of Bone Morphogenetic Protein (BMP) treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases were found to be upregulated in response to BMP4 treatment. [PLoS One] Full Article

Mitochondrial Bioenergetics of Metastatic Breast Cancer Cells in Response to Dynamic Changes in Oxygen Tension: Effects of HIF-1α
A novel experimental approach was developed to examine the real-time bioenergetic changes in breast cancer cells (BCCs) during adaptation to oxygen tension using sensitive extracellular flux technology. Oxygen was gradually removed from the medium, and the bioenergetics of metastatic BCCs was compared with non-tumorigenic cells. [PLoS One] Full Article


Trastuzumab Emtansine in the Treatment of HER-2-Positive Metastatic Breast Cancer Patients
Trastuzumab emtansine is a HER-2-targeted antibody-drug conjugate, composed of the cytotoxic microtubule polymerization inhibitor DM1 that is conjugated to the monoclonal antibody trastuzumab, able to selectively deliver a cytotoxic agent to HER-2-positive tumor cells. TDM-1 is superior and less toxic than lapatinib plus capecitabine in metastatic breast cancer patients previously treated with trastuzumab and taxanes, and its role as a first-line therapy is currently under investigation. [Future Oncol] Abstract

Clinicopathological Features Among Patients with Advanced Human Epidermal Growth Factor-2-Positive Breast Cancer with Prolonged Clinical Benefit to First-Line Trastuzumab-Based Therapy: A Retrospective Cohort Study
Scientists investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. [Clin Breast Cancer] Abstract

Watch Video: Learn How to Enumerate Mammospheres and Tumorspheres Cultured in MammoCult™
Benzyl Isothiocyanate: Double Trouble for Breast Cancer Cells
Researchers show that benzyl isothiocyanate (BITC) inhibits breast cancer stem cell growth, both in vitro and in vivo, in association with suppression of the full-length receptor tyrosine kinase RON as well as its activated truncated form, both of which seem to drive stemness in breast cancer cells. This perspective briefly reviews epidemiologic evidence, preclinical efficacy data, and molecular and cellular mechanistic attributes of BITC. Critical issues relevant to clinical development of BITC are discussed briefly. [Cancer Prev Res] Abstract

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Grants Help Fight Breast Cancer
Fourteen Kentucky agencies promoting breast cancer awareness, screening and access to services are this year’s recipients of grants from the Kentucky Breast Cancer Research and Education Trust Fund. The trust fund, administered by the Department for Public Health in the Cabinet for Health and Family Services, recently announced the grant awards, totaling over $278,000. [Commonwealth of Kentucky] Press Release

FDA Grants Genentech’s Perjeta Regimen Priority Review for Use Before Surgery in HER2-Positive Early Stage Breast Cancer
Genentech, a member of the Roche Group, announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application for the use of a Perjeta® (pertuzumab) regimen before surgery (neoadjuvant treatment) in people with HER2-positive early stage breast cancer. The FDA has granted a Priority Review of the application and will make a decision on approval by October 31, 2013. [Genentech, Inc.] Press Release

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Therapeutic Goods Administration (Australia)
NEW IMPAKT 2014 Breast Cancer Conference
May 8-10, 2014
Brussels, Belgium

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NEW Postdoctoral Fellow – Breast Cancer Cell Research (Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellowship – Regulation and Functions of Long Noncoding RNAs in Mammary Cell Growth and Differentiation (Universita’ degli Studi di Torino)

Postdoctoral Fellowship – Breast Cancer (Bellvitge Biomedical Research Institute [IDIBELL])

Postdoctoral Fellow – Breast Cancer Research (Albert Einstein College of Medicine)

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)

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 Metastasis (Weizmann Institute of Science)

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

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