Phosphatidylinositol 3-Kinase and Protein Kinase C as Molecular Determinants of Chemoresistance in Breast Cancer
Abstract
The goal of this project is to identify novel therapeutic strategies aimed at counteracting or reversing drug resistance in breast cancer. Chemotherapeutic drug resistance may result, in part, from a shift in the regulation of cellular mechanisms away from apoptosis to a more survival-oriented pathway. Two proteins that have been implicated as anti-apoptotic are protein kinase C and phosphatidylinositol 3-kinase. Although differential expression of these kinases have been linked to anti-apoptotic signaling mechanisms, the molecular details of upstream and downstream events are not well understood, and therefore elucidation of their mechanisms of action may represent a potential therapeutic target for breast cancer. Using an isogenic model system of estrogen receptor positive, apoptosis-sensitive and apoptosis-resistant breast cancer cell variants, this proposal aims to define the role of phosphatidylinositol 3-kinase and specific protein kinase C isoforms in cellular apoptotic signaling pathways. We have found that PKC a and 8 isoforms are differentially expressed in our isogenic model. We are currently optimizing the use of green fluorescent protein-tagged, as well as constitutive-active and dominant-negative, PKC constructs, in order to better understand how PKC and PI3K may affect survival and apoptotic signaling in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA409382
Entities
People
- Amanda P. Parker
- Barbara S. Beckman
- Matthew Burow
Organizations
- Tulane University of Louisiana