Mechanism for Controlling Breast Cancer Growth and Skeletal Metastasis
Abstract
The effect of bone morphogenetic protein-2 (BMP-2) on breast cancer cell growth was not known at the time of our study. During past three years we systematically investigated the role of BMP-2 on human breast cancer cell growth and the underlying mechanism. The aim was to identify novel therapeutic application for BMP-2 in breast cancer cell growth inhibition. We showed that BMP-2 inhibits the growth of both estradiol-sensitive (MCF-7) and insensitive (MDA MB 231) human breast cancer cells. Next we demonstrated that BMP-2 inhibits estradiol-induced growth of both MCF-7 and MDA MS 231 cells by inhibiting mitogen activated protein kinase (MAPIC) activity. In addition BMP-2 also induced phosphorylation of retinoblastoma protein (pRb) . Phosphorylated pRb is a potent inhibitor for cell cycle progression. Thus we show that BMP-2 intercepts cell signaling for growth of cancer cells by two very powerful mechanisms. Since our goal was to use BMP-2 therapeutically, we showed that adenovirus-directed BMP-2 expression inhibits breast tumor growth in an animal model. In addition, we wanted to study the role of BMP-2 on bone metastasis of breast cancer cells, since one of the biggest problems associated with breast cancer is its secondary localization to bone. Currently we are designing experiments towards this goal and are testing them as a long term extension of this project.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA405487
Entities
People
- Nandini Glosh-choudhury
Organizations
- University of Texas Health Science Center at San Antonio