ER(alpha) and ErbB-2 Cross-Talk in Mammary Tumorigenesis and Metastasis
Abstract
The interaction between growth factor and steroid hormone receptors may play a critical role in the breast cancer progression. The principle objective of this proposal is to elucidate the in vivo importance of cross-talk between estrogen and ErbB-2 signaling pathways. We first plan to establish transgenic mice that express both an constitutively active estrogen receptor and its co-activator in the mammary epithelium. To accomplish this objective, we will derives eparate strains of transgenic mice that carrying either a constitutively activated ER or its co-activatorAIB1 under the transcriptional control of the mouse mammary tumor virus (MMTV) promoter enhancer. Once these transgenic strains have been derived we will assess whether activation of estrogen signaling pathway can either positively or negatively influence ErbB-2 mediated tumor progression by interbreeding these strains to separate strains of transgenic mice expressing an activated erbB-2 oncogene in the mammary epithelium. Because activation of estrogen signaling pathway is known to influence the transcriptional activity of the erbB-2 promoter, we plan to use a unique ErbB-2 mammary tumor model in which mammary epithelial expression of the ErbB-2 oncogene is under the transcriptional control of the endogenous ErbB-2 promoter. The results of these studies will provide important insight into these crucial signaling pathways in breast cancer progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425125
Entities
People
- William Muller
Organizations
- McGill University