Mammary Cell News Volume 4.39 | Oct 4 2012

LABORATORY RESEARCH

Loss of SNAIL Regulated miR-128-2 on Chromosome 3p22.3 Targets Multiple Stem Cell Factors to Promote Transformation of Mammary Epithelial Cells
Enforced expression of microRNA-128 (miR-128) impeded several oncogenic traits of mammary carcinoma cells, whereas depleting miR-128-2 expression was sufficient for oncogenic transformation and stem cell-like behaviors in immortalized non-tumorigenic mammary epithelial cells, both in vitro and in vivo. [Cancer Res] Abstract

ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells
Researchers report that ICOS, a T cell co-stimulatory molecule of the CTLA4/PD1/CD28 family, is expressed mostly by tumor-associated regulatory T cells (Treg) in primary breast tumors. A large proportion of these ICOS+ Treg were Ki67+ and this evident proliferative expansion was found to rely upon interactions with tumor-associated plasmacytoid dendritic cells. [Cancer Res] Abstract

Inhibition of TGF-ß/Smad Signaling by BAMBI Blocks Differentiation of Human Mesenchymal Stem Cells to Carcinoma-Associated Fibroblasts and Abolishes Their Pro-Tumor Effects
BMP and Activin Membrane Bound Inhibitor (BAMBI)-transduction significantly inhibited transforming growth factor ß (TGF-ß)/Smad signaling and expression of Carcinoma-associated fibroblast markers in human bone marrow mesenchymal stem cells (BM-MSCs) treated with TGF-ß1 or tumor conditioned medium or co-cultured with cancer cells, but did not alter the stem cell properties and the tumor-tropic property of MSCs. In addition, BAMBI-transduction disrupted the cytokine network mediating the interaction between MSCs and breast cancer cells. [Stem Cells] Abstract
 
Depletion of Plasmacytoid Dendritic Cells Inhibits Tumor Growth and Prevents Bone Metastasis of Breast Cancer Cells
Using three immunocompetent mouse models of breast cancer bone metastasis, scientists identified a key role for plasmacytoid dendritic cells in facilitating tumor growth through immunosuppression and aggressive osteolysis. [J Immunol] Abstract

HDAC11 is a Novel Drug Target in Carcinomas
Scientists report that histone deacetylase 11 (HDAC11) is overexpressed in several carcinomas compared to corresponding healthy tissues. HDAC11 depletion is sufficient to cause cell death and to inhibit metabolic activity in HCT-116 colon, PC-3 prostate, MCF-7 breast and SK-OV-3 ovarian cancer cell lines. [Int J Cancer] Abstract

Regulation of COX2 Expression in Mouse Mammary Tumor Cells Controls Bone Metastasis and PGE2-Induction of Regulatory T Cell Migration
Due to the strong connection of cyclooxygenase 2 (COX2) with immune function, researchers focused on understanding how variance in COX2 expression manipulates the immune profile in a syngeneic, and immune-competent, mouse model of breast cancer. Though there have been correlative findings linking elevated levels of COX2 and Tregs in other cancer models, the researchers sought to elucidate the mechanisms by which these immuno-suppressive cells are recruited to breast tumor and the means by which they promote tumor tolerance. [PLoS One] Full Article

Disruption of 3D MCF-12A Breast Cell Cultures by Estrogens – An In Vitro Model for ER-Mediated Changes Indicative of Hormonal Carcinogenesis
Scientists describe an in vitro three dimensional (3D) model for breast glandular structure development, using breast epithelial MCF-12A cells cultured in a reconstituted basement membrane matrix. These cells were estrogen receptor (ER)α, ERβ and G-protein coupled estrogen receptor 1 competent, allowing the investigation of the effects of estrogens on mammary gland formation and disruption.
[PLoS One] Full Article

CLINICAL RESEARCH

The Prognostic Role of TGF-ß Signaling Pathway in Breast Cancer Patients
Tumors with high expression of transforming growth factor-ß (TGF-ß) receptor II (TßRII), TßRI and TßRII, and phosphorylated-Smad2, and low expression of Smad4 had an unfavorable prognosis concerning progression-free survival. [Ann Oncol] Abstract

Progesterone Receptor Loss Identifies Luminal B Breast Cancer Subgroups at Higher Risk of Relapse
Scientists explored patterns of recurrence in women with breast cancer defined as Luminal B (estrogen receptor-positive and/or progesterone receptor-positive, HER2 positive and/or Ki-67=14%) by immunohistochemical classification. [Ann Oncol] Abstract

Impact of Hormone Receptor Status on Patterns of Recurrence and Clinical Outcomes among Patients with Human Epidermal Growth Factor-2-Positive Breast Cancer in the National Comprehensive Cancer Network: a Prospective Cohort Study
Researchers found that presenting features, patterns of recurrence and survival of human epidermal growth factor-2-positive breast cancer differed by hormone receptor status. [Breast Cancer Res]
Full Article | Press Release

GTx Announces Sale of Fareston^®
GTx, Inc. announced that it has sold to ProStrakan Group plc its rights and related assets in the metastatic breast cancer product, Fareston^®, for total cash consideration of $21.7 million. After deducting cash expenses relating to the transaction, GTx will receive net cash proceeds from the sale of approximately $19 million. [GTx, Inc.] Press Release

One In Two Women Newly Diagnosed With Breast Cancer Reaches Out to the American Cancer Society for Help and Support
An analysis by the American Cancer Society shows one out of two women diagnosed with breast cancer turns to the Society for help and support. The American Cancer Society estimates that in 2012, there will be 226,870 new cases of invasive breast cancer and 39,510 deaths from breast cancer among women in the U.S. This October, the Society will be using National Breast Cancer Awareness Month to remind women about the importance of breast health. [American Cancer Society] Press Release

Phenogen Sciences Announces Immediate Availability of BREVAGen™ Breast Cancer Risk Assessment Test in 49 of 50 States
Phenogen Sciences, Inc. announced the immediate availability of BREVAGen™, a predictive risk test for the millions of women at above average risk of developing estrogen-receptor positive breast cancer. [Phenogen Sciences, Inc.] Press Release

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NEW Lorne Cancer Conference
February 14-16, 2013
Victoria, Australia

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Research Technologist – Research and Development (STEMCELL Technologies, Inc.)

Scientific Communications & Publishing Coordinator (STEMCELL Technologies, Inc.)

Product Manager – Hematopoietic (STEMCELL Technologies, Inc.)

Assistant Professor – Breast Cancer Research (Johns Hopkins University)

Postdoctoral Position – Stem Cell/Cancer/Developmental Biology (Tufts University School of Medicine)

Postdoctoral Fellow – Gene Regulation in Breast Cancer/Stem Cell Biology (University of Cincinnati)

Associate Attending Breast Pathologist (Memorial Sloan-Kettering Cancer Center)

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