Interaction Between Estrogen Receptor-beta and the Transforming Growth Factor-beta Signaling Cascade in Human Breast Tissue

Abstract

The overall goal of this research is to understand the importance of the interaction between Smad3 and the estrogen receptor (ER) as it pertains to human breast tumorigenesis and breast cancer progression. Preliminary data from our laboratory had suggested that ERalpha, ERbeta1, ERbeta2 and ERbeta5 interact with Smad3 in the yeast two-hybrid system. Our current data suggests that a weak interaction between ERalpha and ERbeta1 with Smad3 exists in vitro but not in vivo. Furthermore, although Smad3 does not affect ER transcriptional activity on a vitellogenin ERE, both ERalpha and ERbeta1 inhibit Smad3 transcriptional activity on the p3TP-Lux reporter in Cos1 cells. However, the ERbeta variants, ERbeta2 and ERbeta5 did not affect Smad3 transcription. We are currently in the process of confirming these results in a human breast cancer cell line. Overall, the data support the hypothesis that ER interacts with the TGFbeta signal transduction pathway. The possible mechanisms by which ER affects Smad3 transcription are being investigated.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2002
Accession Number
ADA407175

Entities

People

  • Tracy C. Cherlet

Organizations

  • University of Manitoba

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DTIC Thesaurus Topics

  • Abstracts
  • Biomedical Research
  • Biomolecules
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Compounds
  • Electronic Mail
  • Estrogens
  • Growth Factors
  • Manitoba
  • Peptide Growth Factors
  • Peptides
  • Proteins
  • Tumor Cell Line
  • Universities

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  • Breast cancer cell signaling and growth regulation.