Androgen Regulation of p27 in the Normal and Neoplastic Prostate

Abstract

Hypothesis and rationale: The hypothesis of the proposal is that the cyclin-dependent kinase inhibitor p27 is regulated by androgens in both normal and neoplastic prostate. We also hypothesized that regulation occurs primarily by ubiquitin mediated degradation. This pathway affects both p27 ubiquitination (leading to degradation) and de-ubiquitination. The latter is thought to result from increased activity of de-ubiquitinating enzymes or isopeptidases, which stabilize protein targets. Specific Aim 1: To determine whether testosterone (T) regulates the expression of p27 in normal and neoplastic prostate. Specific Aim 2: To study expression of p27 in androgen-dependent (AD) and androgen- independent (M) human prostate cancer. Specific Aim 3: To study the role of isopeptidases in ubiquitin-proteasome dependent degradation of p27 in androgen-mediated proliferation. Specific Aim 4: To assess the role of isopeptidases in prostate cancer cell proliferation and G1 arrest in LNCaP cells.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1999
Accession Number
ADB259637

Entities

People

  • Massimo Loda

Organizations

  • Dana–Farber Cancer Institute

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Androgen Receptors
  • Androgens
  • Biomedical And Dental Materials
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Epithelial Cells
  • Health Services
  • Neoplasms
  • Polymerase Chain Reaction
  • Prostate
  • Prostate Cancer
  • Proteins
  • Tissues

Fields of Study

  • Biology
  • Chemistry
  • Medicine

Readers

  • Molecular Biology and Genetics
  • Prostate Cancer Biology.