LABORATORY RESEARCH Reduced Formation of Depurinating Estrogen-DNA Adducts by Sulforaphane or KEAP1 Disruption in Human Mammary Epithelial MCF-10A Cells Sulforaphane (SFN) may alter estrogen metabolism and thus protect against estrogen-mediated DNA damage and carcinogenesis. Human breast epithelial MCF10A cells were treated with either vehicle or SFN and either estradiol (E2) or its metabolite 4-OHE2. 4-Hydroxy derived estrogen metabolites and depurinating DNA adducts formed from E2 and its interconvertable metabolite estrone were analyzed by mass spectrometry. [Carcinogenesis] Abstract Targeting Mutant p53 by a SIRT1 Activator YK-3-237 Inhibits the Proliferation of Triple-Negative Breast Cancer Cells Investigators report a small molecule compound YK-3-237 that reduces acetylation of mtp53 and exhibits anti-proliferative effects toward triple-negative breast cancer cells carrying mtp53. YK-3-237 activates SIRT1 enzyme activities in vitro and deacetylation of both mtp53 and wild type p53 in a SIRT1-dependent manner. [Oncotarget] Abstract DAX-1, as an Androgen-Target Gene, Inhibits Aromatase Expression: A Novel Mechanism Blocking Estrogen-Dependent Breast Cancer Cell Proliferation The authors demonstrated, in hormone-dependent breast cancer cells, the existence of a functional interplay between the androgen receptor, the orphan nuclear receptor DAX-1 and the aromatase enzyme involved in the inhibition of the estrogen-dependent breast cancer cell proliferation exerted by androgen signaling. [Cell Death Dis] Full Article Identification of Sirtuin 3, a Mitochondrial Protein Deacetylase, as a New Contributor to Tamoxifen Resistance in Breast Cancer Cells Scientists showed that Sirtuin 3 (SIRT3) was significantly up-regulated at both mRNA and protein levels in the tamoxifen (Tam)-resistance human breast cancer cell line MTR-3, which was derived from MCF-7 line by continuous selective culture in the presence of 1 μM of Tam for two years. They further demonstrated that SIRT3 was rapidly up-regulated in the sensitive MCF-7 cells following exposure to Tam. [Biochem Pharmacol] Abstract Quantitative Proteomic Analysis of HER2 Normal and Overexpressing MCF-7 Breast Cancer Cells Revealed Proteomic Changes Accompanied with HER2 Gene Amplification Researchers studied the proteomic changes that accompany the HER2 gene amplification to identify potential new therapeutic targets and biomarkers. They analyzed bio-triplicate proteome samples extracted from wild-type MCF-7 human breast cancer cells and their isogenic stably overexpressing HER2 (amplified) transfectants. [J Proteomics] Abstract Steroidal Aromatase Inhibitors Inhibit Growth of Hormone-Dependent Breast Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis Scientists evaluated the effects of several steroidal aromatase inhibitors, namely 3β-hydroxyandrost-4-en-17-one, androst-4-en-17-one, 4α,5α-epoxyandrostan-17-one and 5α-androst-2-en-17-one, on cell proliferation, cell cycle progression and cell death in an estrogen receptor positive aromatase-overexpressing human breast cancer cell line. [Apoptosis] Abstract Curcumin Enhances TRAIL-Induced Apoptosis of Breast Cancer Cells by Regulating Apoptosis-Related Proteins Researchers found that the combination of TNF-related apoptosis inducing ligand (TRAIL) with curcumin can synergistically induces apoptosis in three TRAIL-resistant breast cancer cell lines. The mechanism behind this synergistic cell death was investigated by examining an effect of curcumin on the expression and activation of TRAIL-associated cell death proteins. [Mol Cell Biochem] Abstract Estrogen Induced Concentration Dependent Differential Gene Expression in Human Breast Cancer (MCF7) Cells: Role of Transcription Factors Meta-analysis of the expression data of MCF7 cells treated with low or high dose of estradiol was performed. Investigators identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. [Biochem Biophys Res Commun] Abstract CLINICAL RESEARCH Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer Scientists performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated metastatic breast cancer. [J Clin Oncol] Abstract Circulating Tumor Cells Predict Progression-Free and Overall Survival in Chinese Patients with Metastatic Breast Cancer, HER2-Positive or Triple-Negative (CBCSG004): A Multicenter, Double-Blind, Prospective Trial This study evaluated the potential utility of circulating tumor cell measurements in predicting responses to anticancer therapies, including response to human epidermal growth factor receptor-2 (HER-2)-targeted agents, progression-free survival, and overall survival in Chinese women with metastatic breast cancer. [Ann Oncol] Abstract |