Inducible Transgenic Models of BRCA1 Function

Abstract

Germline mutations in the breast and ovarian cancer susceptibility gene BRCA1, account for a large proportion of families with inherited breast and ovarian cancer. Interestingly, while germline BRCA1 mutations predispose carriers to adenocarcinoma of the breast, no somatic BRCA1 mutations have been found in sporadic primary breast cancers. This observation suggests that this molecule may normally protect the breast against carcinogenesis only during specific stages of mammary gland development. Previously, we have analyzed the temporal and spatial pattern of Brca1 expression during normal mouse embryogenesis, in adult tissues, and during postnatal mammary gland development. These studies support a role for Brca1 in the regulation of cell proliferation and differentiation in the breast during puberty and pregnancy. We hypothesize that Brca1 plays a critical role in mammary gland development, and that its function is temporally restricted to particular developmental phases. During the course of this project, we have developed a novel tetracycline-inducible expression system to test this hypothesis in transgenic mice. This approach has contributed to our ability to determine how the loss or mutation of this molecule contributes to carcinogenesis in a developmental-specific manner.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2000
Accession Number
ADB267620

Entities

People

  • Lewis A Chodosh

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Brain
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Genetics
  • Health Services
  • Medical Personnel
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.