Rb Associated Protein 46: Roles in Progression of Proliferation Breast Cancer
Abstract
Our research program is focused on Rb associated protein 46 (RbAp46), a novel tumor suppressor gene that we recently identified and cloned. Our major goal is to understand the role of RbAp46 in the early development of breast cancer. During the project period (2000-2003), we accomplished all of the tasks proposed in our application. We demonstrated RbAp46 tumor suppressor function in the early development of breast cancer, revealing cellular and molecular mechanisms by which RbAp46 functions as a tumor suppressor. Using MCFl0AT3B cells derived from a xenograft model of human proliferative breast disease, we discovered that RbAp46 overexpression strongly inhibits abnormal growth and tumorigenicity of neoplastigemc MCFl0AT3B cells. RbAp46 overexpression also facilitates stress-induced apoptosis in MCFl0AT3B cells through consistent activation of the JNK/SAPK pathway. We also found that restoration of RbAp46 expression in breast cancer cells strongly inhibits malignant features of these tumor cells. Importantly, we found that inducible RbAp46 expression in established breast cancer xenografts strongly suppressed progressive growth of breast cancer in vivo. Furthermore, we demonstrated that constitutive RbAp46 expression in MCFl0AT3B cells inhibits estrogen-stimulated growth of these cells in vitro and tumorigenicity in vivo. Finally, we revealed that several signaling pathways, including the JNK/SAPK pathway and the catenin pathway, are involved in RbAp46 function as a potent tumor suppressor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA420116
Entities
People
- Moshe Yamin
- Zhaoyi Wang
Organizations
- Beth Israel Deaconess Medical Center