Use of a Transgenic Mouse Model With a Regulatable Estrogen Receptor Alpha (ER) to Study the Role of ER in Mammary Gland Development and Cancer

Abstract

Estrogen (E2) is required for the development of breast cancer, but there are few animal models to study its mechanism of action in vivo. We hypothesize that the timing of estrogen receptor alpha (ERalpha) action is crucial in normal mammary gland development and tumorigenesis. Therefore, a transgenic mouse model with a regulatable ERalpha is being generated. In vitro, a mutant ERalpha (525L) has a severely attenuated response to endogenous estradiol (E2) but a wild-type (WT) response to diethylstibestrol (DES). Gene targeting was used to insert 525L into the WT ER gene. Positive clones were injected into mouse blastocysts and chimeras were generated. There has been no germline transmission so far. Additional injections and further breeding continues. The resultant transgenic mouse will enable us to study how the timing of ER activation modulates normal mammary maturation and the development of mammary cancers.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2004
Accession Number
ADA429801

Entities

People

  • Sonia L Sugg

Organizations

  • Medical College of Wisconsin

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Breeding
  • Cancer
  • Chimerism
  • Culture Techniques
  • Embryos
  • Estrogens
  • Genes
  • Genetic Code
  • Genetics
  • Glands
  • Growth Factors
  • Mammary Glands
  • Neoplasms
  • Peptide Growth Factors
  • Universities

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Immunology and Pathology
  • Molecular and genetic basis of cancer.