Selective Gene Regulation by Androgen Receptor in Prostate Cancer

Abstract

Androgen binds to the androgen receptor (AR) and is required for prostate cancer initiation and progression. Although androgen ablation is initially an effective prostate cancer therapy, patients eventually develop resistance, but disease remains driven by AR. There is a need to identify AR gene programs that promote proliferation versus differentiation to design better treatments. Using mutant ARs as models of aberrant AR activity, I generated cell lines harboring wild-type and mutant ARs and analyzed proliferation, anchorage-independent cell growth and alterations in AR target genes. I also generated a multiplexed promoter assay for high-throughput screening (HTS) to identify compounds that selectively regulate AR. After assay optimization, the primary HTS was performed with 2,5000 compounds. A dose response assay identified several compounds that selectively regulate AR and will be further studied in cell-based assays.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2012
Accession Number
ADA568972

Entities

People

  • Elizabeth Lapensee

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Cell Line
  • Cells
  • Diseases And Disorders
  • Gene Expression
  • Hormones
  • Indicator Dyes
  • Molecules
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins
  • Regulations
  • Small Molecules
  • Throughput

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology and Biomarker-Based Cancer Detection.
  • Prostate Cancer Biology.