Role of the APAf-1Caspase-9 Pathway in Breast Tumor Development

Abstract

The Aim of this concept award project was to assess the function of Apaf-1/Caspase-9 in tumorigenesis in the mouse. We planned to use mutant mice (FOG mice) expressing a hypomorphic allele of Apaf-1 gene in the breast as the Apaf-1 KO mutation is embryonic lethal. Crosses of heterozygous FOG+/- mice yielded mostly FOG-I- mice that exhibited major cranial defects and died shortly after birth. Thus, FOG mutant could be not be used to assess the role of Apaf-1 in tumor development in vivo. In parallel studies, we have developed a system to express stably small (21-29 bp) interfering RNAs (siRNAs) targeted against Apaf-1 transcripts. Eight hairpin oligonucleotides were designed to target four different regions of the Apaf-1 transcript. We constructed and tested multiples constructs and identified a RNAi construct that effectively inhibit the expression of Apaf-I protein in breast cancer cells.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2003
Accession Number
ADA420847

Entities

People

  • Gabriel Nunez

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Availability
  • Biomedical Research
  • Breast Cancer
  • Classification
  • Electronic Mail
  • Information Operations
  • Maryland
  • Michigan
  • Monitoring
  • Neoplasms
  • Security
  • Standards
  • Universities

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Molecular and Cellular Biology