Abstract
Breast cancer is one of the leading causes of cancer death in women. The Notch family of proteins plays crucial roles in determining cell fates such as proliferation, differentiation and apoptosis. A role for Notch signaling in human breast cancer has been suggested by the development of adenocarcinomas in the murine mammary gland. However, it is not clear currently whether Notch signaling is frequently expressed and activated in breast cancers. Here we show that Notch signaling is overexpressed and highly activated in breast cancers. More significantly, the attenuation of Notch signaling by gamma-secretase inhibitor can inhibit the proliferation of breast cancer cells by both causing cell cycle arrest and apoptosis. Thus, targeting Notch signaling may be of therapeutic value in breast cancers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amyloid Precursor Protein Secretases / antagonists & inhibitors
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Amyloid Precursor Protein Secretases / metabolism
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Apoptosis / physiology
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Basic Helix-Loop-Helix Transcription Factors / genetics*
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Breast / metabolism
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Breast / pathology
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Calcium-Binding Proteins / genetics*
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Calcium-Binding Proteins / metabolism
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Cell Cycle / physiology
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Cell Line, Tumor
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Cell Proliferation
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins / genetics*
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Intercellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Protease Inhibitors / pharmacology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Neoplasm / genetics
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RNA, Neoplasm / metabolism
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Receptor, Notch1 / genetics
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Receptor, Notch1 / metabolism
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Receptor, Notch3
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Receptor, Notch4
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Receptors, Notch / genetics*
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Receptors, Notch / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Serrate-Jagged Proteins
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Signal Transduction*
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Transcription Factor HES-1
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Up-Regulation
Substances
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Adaptor Proteins, Signal Transducing
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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DLL4 protein, human
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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NOTCH1 protein, human
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NOTCH3 protein, human
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NOTCH4 protein, human
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Protease Inhibitors
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Proto-Oncogene Proteins
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RNA, Messenger
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RNA, Neoplasm
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Receptor, Notch1
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Receptor, Notch3
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Receptor, Notch4
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Receptors, Notch
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Serrate-Jagged Proteins
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Transcription Factor HES-1
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HES1 protein, human
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Amyloid Precursor Protein Secretases