Mammary Cell News Volume 3.06 | Feb 17 2011

Key Culprit Identified in Breast Cancer Metastasis
When doctors discover high concentrations of regulatory T cells in the tumors of breast cancer patients, the prognosis is often grim, though why exactly has long been unclear. Now new research suggests these regulatory T cells produce a protein that appears to hasten and intensify the spread of breast cancer to distant organs and, in doing so, dramatically increase the risk of death. [Press release from the University of California, San Diego discussing online prepublication in Nature]

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A Hunk of a Target for Treating Breast Cancer
By studying mouse models, a team of researchers has now identified a key role for the protein Hunk in the formation of tumors driven by overexpression of HER2. [Press release from EurekAlert! discussing online prepublication in the Journal of Clinical Investigation]

Hunk Is Required for HER2/Neu-Induced Mammary Tumorigenesis
By crossing Hunk^-/- mice with transgenic mouse models for HER2/neu-induced mammary tumorigenesis, investigators report that Hunk is required for primary tumor formation induced by HER2/neu. Knockdown and reconstitution experiments in mouse and human breast cancer cell lines demonstrated that Hunk is required for maintenance of the tumorigenic phenotype in HER2/neu-transformed cells.[J Clin Invest]

The Human DEK Oncogene Stimulates Beta-Catenin Signaling, Invasion and Mammosphere Formation in Breast Cancer
Researchers demonstrate that DEK is highly expressed in breast cancer cells compared with normal tissue, and functionally important for cellular growth, invasion and mammosphere formation. [Oncogene]

Differential Expression of Arrestins Is a Predictor of Breast Cancer Progression and Survival
Examination of the expression of the two nonvisual arrestins, arrestin2 and 3, in various breast cancer cell lines revealed comparable expression of arrestin3 in basal and luminal lines while arrestin2 expression was much higher in the luminal lines compared to the more aggressive basal lines. [Breast Cancer Res Treat]

Identification of Early Molecular Markers for Breast Cancer
By comparing murine markers for the ductal carcinoma in situ (DCIS) of the mammary gland with genes up-regulated in human DCIS-samples scientists were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas. [Mol Cancer]

Response to mTOR Inhibition: Activity of eIF4E Predicts Sensitivity in Cell Lines and Acquired Changes in eIF4E Regulation in Breast Cancer
Estimates of eIF4E activity predict sensitivity to mTOR inhibition in cell lines but breast tumors with high estimated eIF4E activity gain changes in eIF4E regulation in order to enhance resistance. [Mol Cancer]

Stat1 Is a Suppressor of ErbB2/Neu-Mediated Cellular Transformation and Mouse Mammary Gland Tumor Formation
Scientists show that Stat1 tyrosine 701 phosphorylation is increased in human breast tumor cells with elevated levels of ErbB2/HER-2 and in cells transfected with ErbB2/Neu. [Cell Cycle]

Pharmacological Inhibition of Sphingosine Kinase Isoforms Alters Estrogen Receptor Signaling in Human Breast Cancer
Researchers examined the ability of pharmacological inhibition of sphingosine-1-phosphate formation to block estrogen signaling as a targeted breast cancer therapeutic. [J Mol Endocrinol]

Caveolin-1 and Mitochondrial SOD2 (MnSOD) Function as Tumor Suppressors in the Stromal Microenvironment: A New Genetically Tractable Model for Human Cancer Associated Fibroblasts
The human caveolin-1 (Cav-1) deficient fibroblasts that investigators have generated are a new genetically tractable model system for identifying other suppressors of the cancer-associated fibroblast phenotype, via a genetic “complementation” approach. This has important implications for understanding the pathogenesis of triple negative and basal breasts cancers, as well as tamoxifen-resistance in ER⁺ breast cancers, which are all associated with a Cav-1 deficient “lethal” tumor micro-environment, driving poor clinical outcome. [Cancer Biol Ther]

CLINICAL RESEARCH

The MDM2 Promoter SNP285C/309G Haplotype Diminishes Sp1 Transcription Factor Binding and Reduces Risk for Breast and Ovarian Cancer in Caucasians
Comparing MDM2 promoter status among different cohorts of ovarian (n = 1993) and breast (n = 1973) cancer patients versus healthy controls (n = 3646), SNP285C reduced the risk of both ovarian (OR 0.74; CI 0.58–0.94) and breast cancer (OR 0.79; CI 0.62–1.00) among SNP309G carriers. [Cancer Cell]

Cyclin E Amplification/Overexpression Is a Mechanism of Trastuzumab Resistance in HER2⁺ Breast Cancer Patients
To identify potential mechanisms of resistance, researchers established trastuzumab-resistant HER2 amplified breast cancer cells by chronic exposure to trastuzumab treatment. [Proc Natl Acad Sci USA]

Hypoxic Regulation and Prognostic Value of LAMP3 Expression in Breast Cancer
LAMP3 is a newly described hypoxia regulated gene of potential interest in hypoxia-induced therapy resistance and metastasis. The prognostic value of LAMP3 in breast cancer was investigated. [Cancer]

U-Systems Announces Initiation of European Breast Ultrasound Screening Study
U-Systems announced participant enrollment has begun in the European Asymptomatic Screening Study at Capio Saint Göran Hospital, in Stockholm, Sweden. [U-Systems Press Release]

York Cancer Center Patients Part of Landmark Breast Cancer Study
Thirty-eight women from south central Pennsylvania were involved in a national breast cancer study which is expected to have a significant impact on how the disease is treated. [WellSpan Health Press Release]

UT Southwestern Launches Clinical Trial for Treatment of Breast Cancer Using Robotic CyberKnife Technology
Breast-cancer patient Dr. Kristin Wiginton is the first to be treated at The University of Texas (UT) Southwestern Medical Center with high-beam radiation using the Accuray CyberKnife System, which offers improved cosmetic results, less radiation exposure to surrounding tissue and a shorter treatment period. [UT Southwestern Medical Center Press Release]

Susan Band Horwitz, Ph.D., Receives AACR Award for Lifetime Achievement in Cancer Research
Susan Band Horwitz, Ph.D., will receive the Eighth AACR Award for Lifetime Achievement in Cancer Research. Horwitz conducted pioneering research by discovering the mechanism of action of the chemotherapeutic drug paclitaxel (Taxol), which prompted the development of this drug as an important therapy for many common solid tumors, including ovarian, breast, and lung carcinomas. [American Association for Cancer Research Press Release]

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