A Novel Role for C/EBP in Mammary Development and Breast Cancer
Annual rept. 1 Jul 97-30 Jun 98
BAYLOR COLL OF MEDICINE HOUSTON TX
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The objective of this fellowship is to characterize the roles which CEBP alpha and CEBP beta play in normal mammary gland development and breast cancer. In general, CEBP alpha is predominantly expressed at high levels in terminally differentiated, growth arrested cells and the CEBP 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 CEBP family members suppresses transcriptional activity. Consequently, an increase in LIP levels may inhibit terminal differentiation and lead to excessive cellular proliferation. Overexpression of CEBP 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.
- Anatomy and Physiology
- Medicine and Medical Research