Developing Novel Anticancer DNA-Binding Drugs to Disrupt ETS-Mediated Transcription Associated with Breast Cancer: Use of the C-Fos Serum Response Element as a Model System

Abstract

Disregulated transcription factor (TF)-mediated activation of gene expression may play a key role in oncogenesis, especially in breast cancer. Preventing TF/DNA interactions using small molecule DNA-reactive agents can decrease oncogenic gene expression and potentially halt cancer development. Our goal is to improve DNA-binding drugs' abilities to inhibit specific TF/DNA interactions using the human c-fos promoter's serum response element (SRE) as a target. The targeted TFs form a ternary complex (TC) on the SRE that is required for induction of c-fos by serum. Classical DNA-binding drugs were first evaluated in order to better understand how sequence selectivities and modes of DNA binding relate to drug effectiveness in inhibiting TF/DNA complexes and resultant transcription.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2000
Accession Number
ADB257291

Entities

People

  • Christine White

Organizations

  • Health Research, Incorporated

Tags

DTIC Thesaurus Topics

  • Albumins
  • Biochemistry
  • Biomedical And Dental Materials
  • Biomedical Research
  • Breast Cancer
  • Cell Physiological Processes
  • Chemistry
  • Gene Expression
  • Glycosides
  • Inhibition
  • Molecular Dynamics
  • Molecules
  • Nucleic Acids
  • Nucleotides
  • Proteins
  • Small Molecules
  • Transcription Factors

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology and Pathology
  • Molecular and genetic basis of cancer.
  • Prostate Cancer Biology.