Differential Mechanisms of Androgen Resistance

Abstract

We proposed to study the mechanisms of androgen resistance by focusing on androgen receptor mutations and may arise due to selective pressures of antiandrogen treatment. We have utilized xenograft and a humanized mouse model of prostate cancer. To date we have identified mutations throughout the androgen receptor coding region and are in the process of carrying out functional analysis. It is proposed that these mutations may lead to greater androgen receptor activity under particular conditions and potentially highlight sites of interaction with critical coactors that might themselves serve as novel therapeutic targets to complement androgen ablation. During this study analysis of tumor progression in the h/mAR X TRAMP mice have highlighted differences in disease course between antiandrogen treated and hormone deplete (castrated) mice. We are in the process of determining mechanisms underlying these differences by characterizing AR levels and subcellular localization in these tumors

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2006
Accession Number
ADA467564

Entities

People

  • Orla A. O'mahony

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Ablation
  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Cancer
  • Carcinoma
  • Cell Line
  • Cells
  • Disease Attributes
  • Diseases And Disorders
  • Hormones
  • Mutations
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Resistance
  • Xenografts

Fields of Study

  • Biology

Readers

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