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/EBpalpha and beta play in normal mammary gland development and breast cancer. In general, C/EBPalpha is predominantly expressed at high levels in terminally differentiated, growth arrested cells and the C/EBPALPHABeta isoforms, most notably LIP, are expressed at high levels' in actively proliferating cells. LIP can act as dominant negative isoform, which when dimerized with other C/EBP family members suppresses transcriptional activity. Consequently, an increase in LIP levels may lead to excessive cellular proliferation. Overexpression of LIP in the mammary gland of transgenic mice results in ductal hyperplasia. Additionally, overexpression of LIP in TM3 mouse mammary cells results in an increase in proliferation via an increase in the number of cells entering S- phase of the cell cycle. Similarly, transplantation of TM3 cells overexpressing LIP into the cleared mammary fat pads of mice also results in very proliferative out- growths. 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, 1999
- Accession Number
- ADA381707
Entities
People
- Cynthia A. Zahnow
Organizations
- Baylor College of Medicine