Effect of Reproductive History on Mammary Epithelial Biology
Abstract
Epidemiologic studies have repeatedly demonstrated that women who undergo a first full-term pregnancy early in life have a significantly reduced lifetime risk of breast cancer. Similar to humans, rodents also display parity-induced protection against breast cancer. We have used high-density DNA oligonucleotide microarrays to identify genes whose expression in the murine mammary gland is persistently altered as a consequence of an early first full-term pregnancy. The panel of differentially expressed genes that we have isolated reproducibly distinguishes between the nulliparous and parous states of the mammary gland in multiple strains of mice and rats. We find that parity results in the persistent down-regulation of multiple genes encoding epithelial growth factors as well as the persistent up-regulation of growth-inhibitory pathways. Our studies further indicate that parity results in a persistent increase in the differentiated state of the mammary gland as well as persistent changes in the immunologic environment and hematopoietic cell types resident within the gland. These data provide the first molecular description of a developmental state of the mammary gland that is associated with reduced cancer risk and suggest novel hypotheses for the mechanistic basis by which parity may modulate breast cancer risk.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADB282174
Entities
People
- Lewis A Chodosh
Organizations
- University of Pennsylvania