Ribozyme Targeting of Steroid Receptor Co-Activators: A Therapeutic Approach to Breast Cancer
Abstract
The gene of the nuclear receptor coactivator AIB1 is amplified in breast cancer cell lines as well as in breast tumor tissue. AIB1 mRNA is often highly expressed in primary breast tumors and is has been shown that AIB1 enhances estrogen and progesterone dependent transcription in vitro. Therefore it has been postulated that AIB1 contributes to the development of breast cancer. However, it is currently not known what the precise role of AIB1 is in the development of breast cancer. To address this question we established MCF-7 breast cancer cell lines in which we can regulate AIBl levels with ribozymes in order to determine the impact of reduced AIB1 gene expression on the phenotype and angiogenic or invasive properties of breast cancer cells. Here we report that depleflon of endogenous AIB1 levels reduced steroid hormone signaling via the estrogen receptor-alpha or progesterone receptor-beta as well as estrogen-mediated inhibition of apoptosis and cell growth. Furthermore, we demonstrate that upon reduction of endogenous AlBl expression, estrogen-dependent colony formation in soft agar and tumor growth of MCF-7 cells in nude mice was decreased. We conclude that AIB1 exerts a rate-limiting role for hormone dependent human breast tumor growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA403442
Entities
People
- Anna T. Riegel
Organizations
- Georgetown University