Role of Nuclear Hormone Receptor Coactivator, E6-Associated Protein (E6-AP) in the Development of Breast Cancer
Abstract
Steroid hormones, estrogen and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivator proteins modulate the biological activity of these hormone receptors. We have cloned an E3 ubiquitin-protein ligase enzyme, E6-associated protein (E6-AP) as a coactivator of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP may contribute to the development of breast cancer. We propose to explore this by developing animal models for overexpression and loss of function of E6-AP and then relate these observations to the clinical setting by studying the expression patterns of E6-AP in various human breast tumor biopsies. In this progress report, we report that we have successfully generated an E6-AP overexpression model. In order to study the effect of loss of function of E6-AP on the normal breast development and breast tumor development, we have acquired an E6-AP null mouse line. These models will be helpful in understanding the role of E6-AP in the development and progression of breast tumors. Presently, we are in the process of breeding and analyzing the mammary gland development of both the overexpression and the loss of E6-AP expression models. Our data from these models suggest that overexpression of E6-AP in mammary gland results in impaired mammary gland development. Furthermore, loss of E6-AP expression results in an overly developed mammary gland compare to that of controls mammary gland. These mice exhibit increased ductal branching and alveolar buds. In order to study the expression profile of E6-AP in human breast tumors, we examined 56 advanced stage human breast cancer biopsy samples. We found an inverse correlation between the expression of E6-AP and the expression of estrogen receptor-alpha in these tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA392051
Entities
People
- Zafar Nawaz
Organizations
- Baylor College of Medicine