The Identification of Estrogen Responsive Genes in the Hypothalamic-Pituitary Axis.

Abstract

Estrogen mediates its biological responses through a specific interaction with the estrogen receptor (ER), an intracellular transcription factor which can bind specific DNA sequences and regulate gene expression. Antagonists to ER, such as tamoxifen, have proven useful in the treatment of ER-positive breast cancer. As tamoxifen has undesirable side effects and resistance to the compound eventually develops, our laboratory has been researching a novel antiestrogen, GW5638. Our goal is to determine if this compound will be useful in the treatment of tamoxifen-refractory breast cancer. We have exploited the MCF-7 athymic mouse model to analyze the effects of GW5638 on this breast cancer cell line. We have found that GW5638 is able to inhibit the development of estrogen-induced breast cancer in this model and may be useful against tamoxifen-resistant tumors. Additionally, our laboratory is interested in the mechanism of action of this compound in bone, as the ability to protect against bone loss is an ideal characteristic of any antiestrogen drug. We have used differential display PCR to screen for genes which may be expressed in response to GW5638 in bone, but identification of such genes has not yet been completed.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 1998
Accession Number
ADA354548

Entities

People

  • Caroline E. Connor

Organizations

  • Duke University Hospital

Tags

DTIC Thesaurus Topics

  • Alkenes
  • Amino Acids
  • Breast Cancer
  • Cell Line
  • Cells
  • Chemistry
  • Estrogens
  • Gene Expression
  • Hormones
  • Identification
  • Neoplasms
  • Osteoporosis
  • Proteins
  • Resistance
  • Side Effects
  • Therapy
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics