Functional and Clinical Analysis of the PTEN Tumor Suppressor Gene in Prostate Cancer
Abstract
The PTEN tumor suppressor gene maps to the 10q23 locus, a chromosomal region frequently altered in prostate cancer. The specific aims of this proposal were to (1) develop high quality antibody reagents to PTEN, (2) to identify downstream targets of PTEN and (3) to study PTEN in primary prostate tumors. We have successfully developed both polyclonal and monoclonal antibodies to PTEN. One antiserum, C54 is a highly specific, sensitive reagent. Data from our lab has shown that the protein product (PTEN), when reconstituted to PTEN -/- cells, induces a cell cycle arrest in G1. This PTEN function requires the ability of FTEN to act as a lipid phosphatase and in so doing functionally antagonize the phosphatidylinositol-3-kinase (PI3K) pathway. In keeping with this notion, a constitutively active form of Akt, a kinase downstream of PI3K, can override a PTEN induced arrest, PTEN can inhibit Akt kinase activity in cells, and PTEN4- tumors have elevated levels of activated Akt. Thus, Akt appears to be a critical downstream target of PTEN. Finally, we have shown that PTEN is lost from 20% of primary prostate cancers by immunohistochemistry. Furthermore, loss of PTEN is highly associated with high Gleason grade and high tumor stage.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADA381167
Entities
People
- William R Sellers
Organizations
- Dana–Farber Cancer Institute