Identification of Novel Drug Targets for Breast Cancer by Designing a Computer Simulation Program to Analyze the Kinetic Process for PIP2 Hydrolysis by PLCgamma
Abstract
PLC gamma 1 hydrolyzes the lipid substrate PIP2 to the two second messengers, IP3 and DAG, in response to certain growth factors, such as EGP. PLC gamma 1 is often overexpressed and activated in breast tumors. Overexpression and activation of PLC gamma 1 in breast tumors have been correlated with increased cell motility, therefore, PLC gamma 1 may play a role in tumor metastasis. As a consequence, PLC gamma 1 is an attractive target for novel anti-cancer therapies. My laboratory proposes to investigate if a computer simulation program can be generated based on existing experimental data, that can predict the kinetic behavior of PLC gamma 1. Creation of an kinetic simulation program for PLC gamma 1 will allow us to predict which steps are rate-limiting and then design experiments to test these predictions. The new experimental data will then be used to refine the simulation program. This approach, if successful, will allow a more rapid identification of potential drug targets. Additional benefit of the program is that it may be able to describe the kinetic behavior of any phospholipase or enzyme, which has been implicated in the progression of breast cancer, that requires binding to the membrane in order to be active.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA410787
Entities
People
- Gwenith Jones
Organizations
- University of Virginia