AKT2 Oncogene and Phosphoinositide 3-Kinase in Human Breast Cancer
Abstract
By screening NCI diversity set that was derived from 140,000 compounds, we have identified several potential Akt inhibitors, one of which has been further characterized and named Akt/PKB inhibitor (API)-2. API-2 specifically inhibited kinase activity of AKT1, AKT2 and AKT3. The inhibition of Akt kinase resulted in suppression of cell growth and induction of apoptosis in human cancer cells that harbor constitutively activated Akt due to overexpression of Akt or other genetic alterations such as PTEN mutation. Furthermore, API-2 potently inhibited tumor growth in nude mice of human cancer cells where Akt is aberrantly expressed/activated but not of those cancer cells where it is not. In addition, we have demonstrated Akt phosphorylation of XIAP to exert its cell survival signal at postmitochondrial level. We have also shown that Akt is targeted by geranylgeranyltransferase I inhibitors (GGTIs).
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA430371
Entities
People
- Jin Q. Cheng
Organizations
- University of South Florida