Phosphoinositide 3-Kinase/AKT1 Pathway and Human Ovarian Cancer
Abstract
Extensive studies have demonstrated that the Akt pathway is essential for cell survival and anti-apoptosis; however, alterations of Akt in human malignancy have not been documented. We have recently demonstrated significantly increased AKT1 and AKT2 kinase activity in primary ovarian carcinomas. We have also shown that PI3K is frequently activated in the specimens with activation of Akt. The majority of cases with PI3K/Akt activation are late stage and high grade. The biological significance of AKTl activation in human cancer was demonstrated by malignant transformation of NIH 3T3 cells transfected with constitutively active AKTl, but not cells transfected with wild type AKT 1. Moreover, inhibition of PI3K/Akt pathway inhibits cell growth and induces apoptosis in human ovarian cancer cell lines. We have also observed that estrogen receptor (ER)a interacts and activates PI3K/Akt pathway. PI3K/Akt feedback regulates ERalpha by phosphorylation of serine-167 of ERalpha. These data indicate that AKT 1 kinase, which is frequently activated in human cancer, is a determinant in oncogenesis and a potential target for cancer intervention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA406214
Entities
People
- Jin Q. Cheng
Organizations
- University of South Florida