Involvement of Steroid Receptor Coactivators/Ubiquitin Pathway Enzymes in Mammary Gland Tumorigenesis
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 coactivators 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 have examined this possibility by studying the expression patterns of E6-AP and estrogen receptor-alpha (ERalpha) in various human breast cancer cell lines and breast tumor biopsy samples. Additionally, we have correlated the expression profile of E6-AP with that of ER in breast tumor biopsies. To date, we have examined 13 samples of invasive breast cancer (IBC), 12 samples of ductal carcinoma in situ (DCIS) and a issue array with 36 different stages breast cancer samples by immuohistochemistry, and 19 samples by immunofluorescence. We found an inverse correlation between the expression of E6-AP and the expression of ER in these tumors. Furthermore, E6-AP is down regulated in invasive breast tumors compared with their adjacent normal tissues, whereas the downregulation of E6-AP was not seen in CIS. The downregulation of E6-AP is stage-dependent. These data suggest a possible role of E6-AP in mammary gland development d tumorigenesis. Presently, we are in the process of creating novel in vitro models in stable cell lines, which will overexpress E6-AP an a controllable manner.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427206
Entities
People
- Xiuhua Gao
- Zafar Nawaz
Organizations
- Baylor College of Medicine