External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator.
Overproduction of the Her2 oncoprotein has been found in approximately 30% of breast tumors, and patients who have Her2 excesses typically have more aggressive disease. Here we show that the expression of the Her2 gene can be decreased by inhibiting the interaction of the two cancer-linked proteins, DRIP130/CRSP130/Sur-2 (a Ras-linked ... subunit of human mediator complexes) and ESX (an epithelial-restricted transcription factor). Disruption of the interaction by a short cell-permeable peptide reduced the expression of the Her2 gene and specifically impaired the growth and viability of Her2-overexpressing breast cancer cells. The association of ESX with DRIP130 is mediated by a small hydrophobic face of an 8-aa helix in ESX, suggesting a therapeutic approach to incapacitating the Her2 gene by small organic molecules.
Mesh Terms:
Amino Acid Sequence, Cell Nucleus, Electrophoresis, Polyacrylamide Gel, Genes, erbB-2, Glutathione Transferase, Hela Cells, Humans, Immunoblotting, Magnetic Resonance Spectroscopy, Mediator Complex, Molecular Sequence Data, Peptides, Protein Binding, Protein Structure, Tertiary, Receptor, erbB-2, Recombinant Fusion Proteins, Time Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, ras Proteins
Amino Acid Sequence, Cell Nucleus, Electrophoresis, Polyacrylamide Gel, Genes, erbB-2, Glutathione Transferase, Hela Cells, Humans, Immunoblotting, Magnetic Resonance Spectroscopy, Mediator Complex, Molecular Sequence Data, Peptides, Protein Binding, Protein Structure, Tertiary, Receptor, erbB-2, Recombinant Fusion Proteins, Time Factors, Trans-Activators, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, ras Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Oct. 01, 2002
PubMed ID: 12242338
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