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- W1574018592 abstract "Abstract : A polypurine tract (PPT) containing multiple GGA repeats in the HER-2/neu promoter is important to control HER-2/neu transcription. We investigated the ability of the PPT to form a G-quadruplex-related secondary structure using biochemical techniques and screened a small family of potential G-quadruplex ligands that could stabilize PPT secondary structure formation in solution. We evaluated several potential lead compounds for their ability to suppress HER-2/neu expression in breast cancer cells. Circular dichroism studies with the distal half of the PPT were similar to findings previously reported for tetrad:heptad DNA. DNA polymerase arrest assays demonstrated potassium induced arrest, and several G-quadruplex interactive compounds that stabilize the HER-2/neu PPT secondary structure were identified from this assay. Telomestatin and a lead compound in the fluoroquinolone class stabilize the HER-2/neu PPT secondary structure in solution and reduce HER-2/neu expression in breast cancer cells. We conclude the HER-2/neu promoter can form a stable secondary structure known as a tetrad:heptad in solution. Compounds that stabilize the tetrad:heptad were identified and some of them reduced HER-2/neu expression in breast cancer cells. Further studies are needed to fully characterize the secondary structure and link the effects of compounds on HER-2/neu expression to their direct interaction with the HER-2/neu promoter." @default.
- W1574018592 created "2016-06-24" @default.
- W1574018592 creator A5005775401 @default.
- W1574018592 date "2005-07-01" @default.
- W1574018592 modified "2023-10-16" @default.
- W1574018592 title "Specific Inhibition of HER-2/Neu Transcription Initiation" @default.
- W1574018592 doi "https://doi.org/10.21236/ada439256" @default.
- W1574018592 hasPublicationYear "2005" @default.
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