Effect of Chimaerins, Novel Receptors for Phorbol Esters, on Breast Cancer Cell Proliferation and Cell Cycle Progression
Abstract
Early studies from our laboratory found that beta2-chimaerin has a Rac-GAP (GTPase-Activating Protein) domain and negatively regulates the activity of Rac, an important small GTPase for the control of cytoskeleton reorganization, cell cycle progression, cell proliferation and malignant transformation. The biological function of chimaerins, however, remains largely unknown. In the second year of my postdoc fellowship, my research work mainly focused on testing our central hypothesis that chimaerin is able to induce cell cycle arrest and inhibit cell proliferation through inactivation of Rac. We found that the mRNA expression levels of beta2-chimaerin in breast cancer cell and tissues are significantly lower than that in normal breast cell and tissues. Expression of beta2-chimaerin impaired the Rac activation by serum and growth factors such as EGF and HRG, reduced cyclin D1 expression and pRb phosphorylation, subsequently induced cell cycle arrest at G1/S phase and inhibited cell proliferation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA442875
Entities
People
- Chengfeng Yang
- Marcelo G Kazanietz
Organizations
- University of Pennsylvania