Mammary Cell News Volume 3.43 | Nov 3 2011

BRCA1 Tumor Suppression Depends on BRCA C Terminus Phosphoprotein Binding, But Not Its E3 Ligase Activity
Scientists found that enzymatically defective breast cancer 1 (Brca1) prevents tumor formation to the same degree as does wild-type Brca1 in three different genetically engineered mouse models of cancer. [Science] Abstract | Press Release

LABORATORY RESEARCH

Cyclin D3 Compensates for the Loss of Cyclin D1 During ErbB2-Induced Mammary Tumor Initiation and Progression
The current work addresses whether cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell cycle regulator can be genetically ablated prior to or after neoplastic transformation. [Cancer Res] Abstract

Dual IGF-1R/InsR Inhibitor BMS-754807 Synergizes with Hormonal Agents in Treatment of Estrogen-Dependent Breast Cancer
Using a model of post-menopausal, estrogen-dependent breast cancer, scientists investigated the anti-tumor effects of the dual insulin like growth factor (IGF)-1R/InsR tyrosine kinase inhibitor BMS-754807 alone and in combination with letrozole or tamoxifen. [Cancer Res] Abstract

Apoptosis Inhibitor ARC Promotes Breast Tumorigenesis, Metastasis and Chemoresistance
In this study, researchers provide evidence of multiple critical pathophysiological functions for ARC (Apoptosis Repressor with Caspase recruitment domain) in breast carcinogenesis. [Cancer Res] Abstract

TGFβ1 Inhibition Increases the Radiosensitivity of Breast Cancer Cells In Vitro and Promotes Tumor Control by Radiation In Vivo
The purpose of this study is to determine whether inhibition of TGFβ signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo. [Clin Cancer Res] Abstract

Identification of a Src Tyrosine Kinase/SIAH2 E3 Ubiquitin Ligase Pathway That Regulates C/EBPδ Expression and Contributes to Transformation of Breast Tumor Cells
Here, scientists have investigated the mechanism(s) regulating CCAAT/enhancer-binding protein delta (C/EBPδ) expression and its role in human breast cancer cells. [Mol Cell Biol] Abstract

TAZ Antagonizes the WWP1-Mediated KLF5 Degradation and Promotes Breast Cell Proliferation and Tumorigenesis
In this study, investigators demonstrated that a transcriptional co-activator with the PDZ binding motif (TAZ) upregulated the krüppel-like factor 5 (KLF5) expression through antagonizing the WWP1-, but not Fbw7-, mediated, KLF5 ubiquitination and degradation. [Carcinogenesis] Abstract

Distinct Patterns of Promoter CpG Island Methylation of Breast Cancer Subtypes Are Associated with Stem Cell Phenotypes
This study was designed to evaluate the promoter CpG island methylation of 15 genes in relation to breast cancer subtype, and to investigate whether the patterns of CpG island methylation in each subtype are associated with their cancer stem cell phenotype represented by CD44⁺/CD24⁻ and ALDH1 expression. [Modern Pathol] Abstract

CLINICAL RESEARCH

A Common Variant at the TERT-CLPTM1L Locus Is Associated with Estrogen Receptor–Negative Breast Cancer
In search of common risk alleles for estrogen receptor (ER)-negative breast cancer, researchers combined genome-wide association study data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. [Nat Genet] Abstract

Moderate Alcohol Consumption During Adult Life, Drinking Patterns, and Breast Cancer Risk
The objective of this study is to evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption. [JAMA] Abstract | Press Release

Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings from the Breast Cancer Family Registry
Investigators estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives. [J Clin Oncol] Abstract | Press Release

Disease-Related Outcomes with Long-Term Follow-Up: An Updated Analysis of the Intergroup Exemestane Study
The protective effect of switching to exemestane compared with continuing on tamoxifen on risk of relapse or death was maintained for at least 5 years post-treatment and was associated with a continuing beneficial impact on overall survival. [J Clin Oncol] Abstract | Press Release

High Levels of Nuclear Heat-Shock Factor 1 (HSF1) Are Associated with Poor Prognosis in Breast Cancer
Findings indicate that HSF1 should be evaluated prospectively as an independent prognostic indicator in estrogen receptor-positive breast cancer. [Proc Natl Acad Sci USA] Abstract | Press Release

Fighting Breast Cancer Early, One Cell at a Time
A team of scientists at Tufts University will develop ultra-sensitive techniques at the single-molecule and single-cell levels designed to detect breast cancer earlier, and treat it with greater precision, through a $6.6 million Innovator Award from the Department of Defense Breast Cancer Research Program made to Tufts chemist David R. Walt. [Tufts University] Press Release

Aeterna Zentaris: FDA Grants IND to Investigator at University of Miami School of Medicine for Phase II Trial with AEZS-108 in Triple-Negative Breast Cancer
Aeterna Zentaris Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Alberto J. Montero, M.D. an Investigational New Drug (IND) approval for the initiation of a randomized Phase II trial in chemotherapy refractory triple-negative luteinizing hormone-releasing hormone receptor (LHRH-R)-positive metastatic breast cancer with the Company’s targeted cytotoxic LHRH analog, AEZS 108. [Aeterna Zentaris Inc.] Press Release

Johns Hopkins Researcher Wins Prize for Breast Cancer Biomarker Studies
A Johns Hopkins breast cancer researcher is the recipient of a $50,000 award designed to encourage rapid translation of her basic research on biomarkers into a commercially available test that could predict the best treatment options for some women with breast cancer. [Johns Hopkins Medicine] Press Release