Mammary Cell News Volume 4.07 | Feb 23 2012

A Novel miR-155/miR-143 Cascade Controls Glycolysis by Regulating Hexokinase 2 in Breast Cancer Cells
Here, scientists show that pro-inflammatory cytokines promote glycolysis in breast cancer cells, and that the inflammation-induced miR-155 functions as an important mediator in this process. [EMBO J] Abstract

Critical Role of Arachidonic Acid-Activated mTOR Signaling in Breast Carcinogenesis and Angiogenesis
Investigators found that the levels of arachidonic acid and cytosolic phospholipase A2 strongly correlated with the signaling activity of mammalian target of rapamycin C1 (mTORC1) and mTORC2 as well as the expression levels of vascular epithelial growth factor in human breast tumor tissues. [Oncogene] Abstract

Coordinate Regulation of Estrogen Receptor β Degradation by Mdm2 and CREB-Binding Protein in Response to Growth Signals
Here, scientists show that activation of ErbB2/ErbB3 tyrosine kinase receptors with growth factor heregulin-β prompts ERβ degradation by the 26S proteasome, a mechanism that requires the coactivator cAMP response element-binding (CREB)-binding protein. [Oncogene] Abstract

Mammary Collective Cell Migration Involves Transient Loss of Epithelial Features and Individual Cell Migration within the Epithelium
Normal mammary morphogenesis involves transitions between simple and multilayered epithelial organization. Researchers used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayer. [J Cell Sci] Abstract

Attenuation of TGF-Beta Signaling Suppresses Premature Senescence in a p21-Dependent Manner and Promotes Oncogenic Ras-Mediated Metastatic Transformation in Human Mammary Epithelial Cells
Here, investigators developed a series of isogenic basal-like human mammary epithelial cells (HMECs) with altered TGF-β sensitivity and different malignancy, resembling a full spectrum of basal-like breast carcinogenesis, and determined the molecular mechanisms that contribute to oncogene-induced transformation of basal-like HMECs when TGF-β signaling is attenuated. [Mol Biol Cell] Abstract

Med1 Plays a Critical Role in the Development of Tamoxifen Resistance
In this report, scientists provide evidence that Med1, an important subunit of mediator coactivator complex, is spontaneously upregulated during acquired tamoxifen-resistance development potentiating agonist activities of tamoxifen. [Carcinogenesis] Abstract

TFF3 Is a Normal Breast Epithelial Protein and Is Associated with Differentiated Phenotype in Early Breast Cancer but Predisposes to Invasion and Metastasis in Advanced Disease
To determine whether TFF3 has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. [Am J Pathol] Abstract | Press Release

The Specific Role of pRb in p16^INK4A-Mediated Arrest of Normal and Malignant Human Breast Cells
In two malignant human breast cancer cell lines, researchers found that individual RB family proteins were sufficient for the establishment of p16-initiated senescence, and that growth arrest in G₁ was not dependent on the presence of functional pRb or p53. [Cell Cycle] Abstract

A Network-Based, Integrative Study to Identify Core Biological Pathways that Drive Breast Cancer Clinical Subtypes
Investigators developed and tested a data-integration method to identify gene networks that drive the biology of breast cancer clinical subtypes. [Br J Cancer] Abstract

Breast Cancer–Associated Abraxas Mutation Disrupts Nuclear Localization and DNA Damage Response Functions
Here, researchers have screened 125 Northern Finnish breast cancer families for coding region and splice-site Abraxas mutations and genotyped three tagging single-nucleotide polymorphisms within the gene from 991 unselected breast cancer cases and 868 female controls for common cancer-associated variants. [Sci Transl Med] Abstract | Press Release

CLINICAL RESEARCH

Responsiveness of Intrinsic Subtypes to Adjuvant Anthracycline Substitution in the NCIC.CTG MA.5 Randomized Trial
Recent studies suggest that intrinsic breast cancer subtypes may differ in their responsiveness to specific chemotherapy regimens. Scientists examined this hypothesis on NCIC.CTG MA.5, a clinical trial randomizing pre-menopausal women with node positive breast cancer to adjuvant cyclophosphamide-methotrexate-fluorouracil vs. cyclophosphamide-epirubicin-fluorouracil chemotherapy. [Clin Cancer Res] Abstract

Phase I Clinical Trial of HER2-Specific Immunotherapy with Concomitant HER2 Kinase Inhibtion
Scientists immunized women (n = 12) with metastatic, trastuzumab-refractory, HER2-overexpressing breast cancer with dHER2, a recombinant protein consisting of extracellular domain and a portion of the intracellular domain of HER2 combined with the adjuvant AS15, containing MPL, QS21, CpG and liposome. Lapatinib (1250 mg/day) was administered concurrently. [J Transl Med] Abstract

Renato Dulbecco, Nobel Laureate and Pioneering Cancer Researcher, Dies at 97
Renato Dulbecco, M.D., Nobel Prize winner and a global leader in cancer research passed away February 19 at his home in La Jolla. [Salk Institute for Biological Studies] Press Release

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