BTG2 Antiproliferative Gene and Prostate Cancer
Abstract
Based on our preliminary findings, the working hypothesis tested in this study was that the tumor suppressive activity of the BTG2 protein is diminished as an early event in prostate carcinogenesis due to increased proteasomal degradation, leading to compromised cell cycle regulation and increased cell invasion. During this study we showed that BTG2 protein expression is lost as an early event in prostate carcinogenesis and that prostate cancer cells degrade BTG2 at a greater rate than noncancerous prostate cells. Steady state levels of BTG2 during the cell cycle appear to regulated by changes in ubiquitination (consistent with proteasomal degradation) and not by changes in the level of the deubiquitinating enzyme USP4. BTG2 has a predominantly nuclear localization consistent with its antiproliferative function, but at 4 hours following growth stimulation of quiescent cells, BTG2 is transiently sequestered in the nucleolus coinciding with transiently reduced rates of degradation (BTG2 is synthesized at similar rates during the cell cycle). Forced expression in PC-3 prostate cancer cells (which do not normally express detectable levels of BTG2) results in increased cell attachment to gelatin, fibronectin and type I collagen substrates. Forced expression in PC-3 prostate cancer cells reduces cell invasion through an extracellular matrix.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2008
- Accession Number
- ADA491607
Entities
People
- Paul D. Walden
Organizations
- New York University