Parity-Induced Protection Against Breast Cancer

Abstract

An early first full-term pregnancy significantly reduces a woman's lifetime risk of developing breast cancer. As such, early first childbirth is one of the most effective naturally occurring protective events that can diminish a woman's risk of breast cancer and is a candidate for targeted chemopreventive strategies. Despite extensive epidemiological evidence in support of parity-induced protection against breast cancer, very little is known about the molecules and pathways responsible for this protective effect. Rodent carcinogenesis models mimic the epidemiology of early parity and provide a valuable system for examining its biological underpinnings. As a means of addressing the underlying molecular and cellular basis of parity induced protection, we have conducted a broad-based gene expression analysis of nulliparous and parous murine mammary glands. As a result of this analysis, we have generated a panel of genes that molecularly define the protected parous mammary gland, including differentiation markers, immune- related genes, growth, factors and TGF-beta3. We identified the upregulation of several differentiation markers for mammary epithelial cells in the parous mammary gland. Additionally, we isolated genes whose expression marks the presence of a permanent population of lymphocytes and macrophages residing in the parous mammary gland. Further analysis of major categories of genes whose expression correlates with the protected parous state revealed a downregulation of multiple growth promoting molecules, such as amphiregulin, insulin-like growth factor, and pleiotrophin, concomitant with an upregulation of growth-inhibitory signaling involving TGF-beta3 and clusterin. To date, these findings represent the most comprehensive analysis of molecular differences induced in the mammary gland by parity.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2000
Accession Number
ADB273020

Entities

People

  • Celina D'cruz
  • Lewis A Chodosh

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Birth
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Dna Microarrays
  • Epithelial Cells
  • Gene Expression
  • Genetic Structures
  • Growth Factors
  • Immune System
  • Lymphocytes
  • Molecules
  • Neoplasms
  • Peptide Growth Factors
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Women's Health and Cancer Risk Research: African American Women and Pregnancy Outcomes.

Technology Areas

  • Biotechnology