A Novel Role for C/EBP in Mammary Development and Breast Cancer
Abstract
The objective of this fellowship is to characterize the roles which C/EBP alpha and C/EBP beta play in normal mammary gland development and breast cancer. In general, C/EBP alpha is predominantly expressed at high levels in terminally differentiated, growth arrested cells and the C/EBP beta isoforms, most notably LIP, are expressed at high levels in actively proliferating cells. LIP can act as a dominant negative isoform, which when dimerized with other C/EBP family members suppresses transcriptional activity. Consequently, an increase in LIP levels may inhibit terminal differentiation and lead to excessive cellular proliferation. Overexpression of C/EBP beta-LIP in the mammary gland of pregnant and lactating transgenic mice results in an abnormal phenotype characterized by enlarged ducts, and regions of hyperplasia. Additionally, preliminary experiments suggest that overexpression of LIP in TM3 mouse mammary cells doubles the growth rate. These observations are consistent with the hypothesis' that increased LIP expression may inhibit terminal differentiation and provide a selective growth advantage facilitating tumor progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA359168
Entities
People
- Cynthia A. Zahnow
Organizations
- Baylor College of Medicine