Downregulation of Breast Cancer Gene Expression by Small Molecule Drugs

Abstract

Over-expression of the HER-2/neu oncogene in breast cancers is associated with aggressive tumor formation, shorter relapse times and higher chemo-resistance. In an effort to transcriptionally downregulate HER-2/neu expression, we have targeted the gene promoter's TATA box with DNA minor groove-binding hairpin polyamides. The DNA-binding specificity and affinity of a 6 bp-binding hairpin polyamide for the Her-2/neu TATA box was determined by the combinatorial method REPSA and confirmed by DNase I footprinting. EMSA studies showed that the hairpin polyamide could inhibit TBP binding to the HER-2/neu TATA box at nanomolar concentrations. A preliminary analysis using a promoter reporter construct in SKBR-3 breast cancer cells revealed that this polyamide molecule could indeed interfere with transcription from the Her-2/neu promoter.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2002
Accession Number
ADA407493

Entities

People

  • Vashisht G. Yennu Nanda

Organizations

  • The University of Texas MD Anderson Cancer Center

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Chemical Synthesis
  • Chemistry
  • Gene Expression
  • Gene Therapy
  • Identification
  • Molecules
  • Neoplasms
  • Phosphodiesterases
  • Proteins
  • Recognition
  • Small Molecules
  • Therapy
  • Transcription Factors

Fields of Study

  • Biology
  • Chemistry

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics
  • Oncology (Cancer Research).