Identification of the Microtubule Inhibitor-Activated Bcl-xL Kinase: A Regulator of Breast Cancer Cell Chemosensitivity to Taxol
Abstract
This training grant set out to define a molecular pathway involved in breast tumor resistance to the key chemotherapeutic class of drugs called microtubule inhibitors (MTIs). It is also designed to train the Principal Investigator (PI) as a future breast cancer physician-scientist. MTIs are the most actively used agents for metastatic and adjuvant BC therapy, yet their use is limited by resistance and side effects. They activate a kinase that phosphorylates and inactivates Bcl-xL, an anti-apoptotic protein that causes resistance to chemotherapeutic agents. The goal is to identify the Bcl-xL kinase first by developing an in vitro assay for it. Previously, we showed that Cdk1/cyclin B1, the master mitotic kinase, phosphorylates Bcl-xL in vitro. Studies here confirm that it also phosphorylates Bcl-xL in cells not only following MTI treatment but also during normal mitosis. Furthermore, preliminary data indicate that Bcl-xL phosphorylation increases tumor cell apoptosis. From there, a clinical research study is underway to study Bcl-xL phosphorylation in patients who have breast cancer and are treated with MTIs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 31, 2010
- Accession Number
- ADA536541
Entities
People
- David Terrano
Organizations
- University of Arkansas for Medical Sciences