EGR-1 Functional Activation, Signaling, and Radiation Response in Prostate Cancer

Abstract

In the grant proposal, we hypothesized that in prostate tumors, radiation will up-regulate pro-survival genes and confer an "induced radiation resistance" phenotype. Overexpression of EGR-1 protein will inhibit radiation-induced pro-survival genes that lead to enhanced radiation-induced apoptosis and tumor regression. Two specific aims were proposed: Aim-1: To determine the functional role of EGR-1 overexpression in the inhibition of radiation-induced pro-survival factors such as NFkB and Bcl-2, and its' impact on radiation response, as judged by tumor regression in prostate cancer cell lines xenografts. Aim-2: To determine the relative effect of radiation on the regression of prostate carcinoma in-situ in TRAMP mice versus TRAMP/Egr-1(-/-)mice. Dimova's resignation (prior PI), I was selected to be the PI of this grant. The following tasks were achieved: Aim 1: Two trials were conducted to assess the impact of Adenoviral EGR-1 therapy in combination with radiation. In Trial 2, tumor tissues were collected for molecular signaling analysis. Aim 2: The breeding of EGR-1 knockout mice and TRAMP mice is in progress. We are currently increasing the population of double transgene TRAMP/EGR-14(-/-) for further experiments. Imaging protocol has been developed and regression of prostate tumor in-situ was assessed in few animals.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2005
Accession Number
ADA438336

Entities

People

  • Mansoor M. Ahmed
  • Marianna Z. Sultanov

Organizations

  • University of Kentucky

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Breeding
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Gene Therapy
  • Genes
  • Genetics
  • Ionizing Radiation
  • Neoplasms
  • Phenotypes
  • Programmed Cell Death
  • Prostate Cancer
  • Radiation
  • Radiation Oncology
  • Radiation Resistance
  • Resistance

Fields of Study

  • Biology
  • Chemistry

Readers

  • Molecular Biology and Genetics