Mammary Cell News Volume 4.37 | Sep 20 2012

T Cells Engineered with a T Cell Receptor against the Prostate Antigen TARP Specifically Kill HLA-A2+ Prostate and Breast Cancer Cells
To produce genetically engineered T cells directed against prostate and breast cancer cells, researchers cloned the T-cell receptor recognizing the HLA-A2-restricted T-cell receptor γ-chain alternate reading-frame protein (TARP)_4-13 epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. [Proc Natl Acad Sci USA] Abstract | Press Release

LABORATORY RESEARCH

p53-Independent Regulation of p21Waf1/Cip1 Expression and Senescence by PRMT6
The authors concluded that protein arginine methyltransferase 6 acts as an oncogene in breast cancer cells, promoting growth and preventing senescence, making it an attractive target for cancer therapy. [Nucleic Acids Res] Full Article

Targeting BRCA1 Localization to Augment Breast Tumor Sensitivity to Poly(ADP-ribose) Polymerase Inhibition
In human sporadic breast cancer cells with functional BRCA1 and proficient double strand break repair, a transient nuclear depletion of BRCA1 and subsequent homologous recombination repair deficit was induced with either truncated BRCA1 or irradiation. This rendered these human sporadic breast cancer cells susceptible to poly(ADP-ribose) polymerase inhibition. [Cancer Res] Abstract | Press Release

Crosstalk Between HER2 and MED1 Regulates Tamoxifen Resistance of Human Breast Cancer Cells
Scientists report that the estrogen receptor coactivator MED1 is a novel crosstalk point for the HER2 and ERα pathways. Their results additionally indicated that MED1 is recruited to the HER2 gene and required for its expression. [Cancer Res] Abstract

ROCK1 Inhibition Promotes the Self-Renewal of a Novel Mouse Mammary Cancer Stem Cell
Researchers discuss the propagation of highly enriched mouse mammary cancer stem cells that retain the potential to differentiate both in vivo and in culture and their use to identify chemical compounds that influence both self-renewal and differentiation. They identified epithelial tumor initiating cells that express lineage markers of both basal and luminal mammary cell lineages and retain the potential, from even single cells, to generate heterogeneous tumors similar to the tumor of origin. [Stem Cells] Abstract

Obesity-Associated Dysregulation of Calpastatin and MMP-15 in Adipose-Derived Stromal Cells Results in their Enhanced Invasion R1
To understand how adipose-derived stromal cells (ASCs) affect breast cancer cells, it is necessary to delineate how they mobilize and home to cancer cells, which requires mobilization and invasion through extracellular matrix barriers. ASCs isolated from the subcutaneous abdominal adipose tissue of obese patients demonstrated increased invasion through Matrigel as well as a chick chorioallantoic membrane, a type I collagen-rich extracellular matrix barrier. [Stem Cells] Abstract

TGFß Induces the Formation of Tumor-Initiating Cells in Claudin^low Breast Cancer
Examiners showed that TGFß increases breast tumor-initiating cell numbers, but only in claudin^low breast cancer cell lines, by orchestrating a specific gene signature enriched in stem cell processes that predicts worse clinical outcome in breast cancer patients. [Nat Commun] Abstract

EZH2 Promotes a Bi-Lineage Identity in Basal-Like Breast Cancer Cells
Investigators showed that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a ‘bi-lineage’ differentiation state, in which cells co-express basal- and luminal-lineage markers. [Oncogene] Abstract

Lipocalin 2 Is a Novel Regulator of Angiogenesis in Human Breast Cancer
The authors had previously reported that Lipocalin 2 (Lcn2) induces the epithelial to mesenchymal transition in breast cancer through the estrogen receptor a/Slug axis and that it is a potential noninvasive biomarker of the disease. Here, they report the novel finding that Lcn2 regulates breast cancer angiogenesis. [FASEB J] Abstract

HuR Is Necessary for Mammary Epithelial Cell Proliferation and Polarity at Least in Part via ΔNp63
Scientists showed that in immortalized MCF10A mammary epithelial cells, HuR knockdown inhibits cell proliferation and enhances premature senescence. They also showed that in three-dimensional culture, MCF10A cells with HuR knockdown form abnormal acini with filled lumen and an aberrant expression pattern of the extracellular matrix protein laminin V. [PLoS One] Full Article

CLINICAL RESEARCH

Epithelial-Mesenchymal Transition and Stem Cell Markers in Patients with HER2-Positive Metastatic Breast Cancer
Scientists assessed the gene transcripts of epithelial-to-mesenchymal transition (EMT) inducing transcription factors and cancer stem cell features in HER2+ metastatic breast cancer (MBC) patients. The data indicated that HER2+ MBC patients have EMT-circulating tumor cells. [Mol Cancer Ther] Abstract

Impact of Breast Cancer Subtypes and Treatment on Survival: An Analysis Spanning Two Decades
Researchers investigated the impact of breast cancer molecular subtypes and treatment on survival in a cohort of medically insured women followed for more than 20 years. Women with HER2-enriched tumors and luminal B subtypes had the poorest survival despite adjusting for important covariates. [Cancer Epidemiol Biomarkers Prev] Abstract | Press Release

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Merrimack Pharmaceuticals to Present Preliminary Clinical Data for Novel Therapies Targeting Molecular Pathways in Advanced Cancers
Merrimack Pharmaceuticals, Inc. announced that research evaluating two novel compounds for advanced cancers, including breast, ovarian, gastric and bladder, will be presented. [Merrimack Pharmaceuticals, Inc.]
Press Release

RaySearch Laboratories: RaySearch Licenses Technology for Automated Treatment Planning from Princess Margaret Cancer Centre
The new agreement, licensed through the Technology Development and Commercialization Office at University Health Network gives RaySearch the right to integrate algorithms and know-how from Princess Margaret Cancer Centre’s technology for automated planning of breast treatments into RaySearch’s RayStation® treatment planning system, where it will be built into the system’s extensive module for automated treatment planning. [Raysearch Laboratories] Press Release

U-Systems’ somo•v Automated Breast Ultrasound System Receives FDA Approval for Breast Cancer Screening
U-Systems announced that the somo•v® Automated Breast Ultrasound (ABUS) system has been approved by the U.S. Food and Drug Administration’s (FDA) for breast cancer screening as an adjunct to mammography for asymptomatic women with dense breast tissue. With the approval, the somo•v ABUS system becomes the only device approved specifically for screening women with dense breasts. [U-Systems] Press Release

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