USF-2 as an Inhibitor of Mammary Gland Carcinogenesis

Abstract

The hypothesis tested in these studies is that overexpression of USF in the mammary glands of transgenic mice will inhibit myc-dependent tumorigenesis. Expression of a FLAG-tagged form or USF-2 was targeted to the mammary gland under the control of the mouse mammary tumor virus (mmtv) long terminal repeat. Of eight lines of transgenic mice that were generated, one demonstrated expression of flag-tagged USF-2 in the lactating mammary gland at levels 12-fold over that of endogenous USF-2. Evaluation of tumorigenesis in these mice (n=17) out to 453 days of age suggests that USF-2 when overexpressed by itself is not oncogenic. In contrast, 72% of mmtv-myc mice (n=18) analyzed have developed mammary tumors with an average latency of 156+/-33 days. Tumor frequency and latency in bigenic mmtv-USF-2/mmtv-C-myc mice out to 200 days of age was similar to that in mmtv-C-myc mice. In contrast the growth of these myc-dependent tumors in bigenic mice was significantly lower (P<O.O1) than that in mmtv-C-myc mice. This decreased growth, however was not associated with changes in cell proliferation or death. These data support the conclusion that while overexpression of USF-2 has only modest impact on mammary gland development and myc-dependent tumorigenesis.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2003
Accession Number
ADA420853

Entities

People

  • Darryl L. Hadsell

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Cell Physiological Processes
  • Cell Size
  • Cells
  • Culture Techniques
  • Epithelial Cells
  • Frequency
  • Glands
  • Inhibitors
  • Mammary Glands
  • Medical Personnel
  • Neoplasms
  • Polymerase Chain Reaction
  • Proteins
  • Terminals
  • Tissue Extracts
  • Transcription Factors

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics