Dysregulation of cellular signaling by HER2/neu in breast cancer☆
Section snippets
HER2/neu disrupts cell-cycle regulation
In eukaryotes, cell-cycle transitions are carefully orchestrated by the ordered assembly and activation of several conserved cyclin-dependent kinase (CDK) complexes. Cyclin-dependent kinase function is regulated by the levels of cyclin, the formation of cyclin-CDK complexes, the phosphorylation of CDK kinase, the subcellular localization of cyclin-CDK complexes, and by two families of cell-cycle inhibitory proteins (known as CDK inhibitors).10 Thus, the cyclin-CDK complexes are the ultimate
HER2/neu disrupts the tumor suppressor p53-MDM2-ARF pathway
The p53 tumor suppressor protein regulates the response of mammalian cells to stress and damage through the transcriptional activation of genes involved in cell-cycle control and apoptosis. Disruption of any of these processes can allow cells to escape growth constraints and apoptosis, and permit the passage of mutations from one generation to the next.23, 24, 25, 26, 27, 28, 29 Evidence for the tumor suppressor function of p53 comes from studies showing that tumors develop with a high
Wnt signaling and HER2/neu induce mammary tumorigenesis via β-cantenin
β-catenin, a member of the armadillo repeat protein family, plays a pivotal role in cell adhesion and Wnt signaling.50 In adherent junctions of cell-cell contacts, β-catenin bridges directly between the cytoplasmic domain of E-cadherin and the actin cytoskeleton through its interaction with β-catenin. In Wnt signaling, binding of soluble Wnt ligands to the Frizzled receptor results in the inactivation of GSK-3β, which normally phosphorylates β-catenin and regulates its ubiquitination and
NF-κB pathways in breast cancer
The NF-κB family of transcription factors consists of p65 (RelA), p50, c-Rel, RelB, and p52 subunits, which can dimerize in various combinations and are activated by a variety of stimuli, including cytokines and oncoproteins. Transient activation of NF-κB in response to the stimulation of cytokines occurs as an inflammatory response; however, sustained activation of NF-κB has been implicated in the pathogenesis of cancer and autoimmune disease.61, 62 In unstimulated cells, the majority of NF-κB
HER2/neu is a potential antitumor target
Breast cancer is a heterogeneous disease with different mutations in either tumor suppressor genes or oncogenes. The effectiveness of the treatment of breast cancer depends on the early diagnosis and quality of classification of the disease that is used to predict the patient’s response to various therapies. With the advance of microarray methods to analyze DNA, RNA, and proteins from breast cancer samples, new methods have developed to refine the early diagnosis and classification of breast
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Antibody-directed metal-organic framework nanoparticles for targeted drug delivery
2020, Acta BiomaterialiaCitation Excerpt :As can be seen, the CMD adsorption led to almost complete restoration of the initial value of the ζ-potential and of the colloidal stability of Fe3O4@MIL-100@CMD nMOFs. For fabrication of the antibody-directed nMOFs, we chose the highly clinically-relevant target, namely, HER2/neu cell surface marker – a membrane protein of the EGFR/ErbB epidermal growth factor receptor family, which is an important prognostic factor for diagnostics and therapy of certain aggressive types of breast cancer [67,68]. Accordingly, we used humanized Trastuzumab anti-HER2/neu antibody for the targeting.
Radiogenomic analysis of prediction HER2 status in breast cancer by linking ultrasound radiomic feature module with biological functions
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Supported by National Institutes of Health grant nos. CA 58880, CA 77858, and CA 78633; by a SPORE grant in ovarian cancer (CA 83639) (M.-C. H.); and by the Nellie Connally Breast Cancer Research Fund at The University of Texas M. D. Anderson Cancer Center (M.-C. H.).