Inhibition of PKR Activity is Required for Survival of Breast Cancer
Abstract
PKR is an interferon-inducible protein kinase, which has recently been discovered to have pleiotropic effects on the growth and differentiation of normal and neoplastic cells. We reported a direct correlation between PKR expression and differentiation in a variety of human tumors and in normal squamous epithelial, and an inverse association between%PKR expression and proliferation in head and neck cancer. The mechanisms by which PKR produced such effects are being intensively studied. Phosphorylation of its major substrate, eIF-2alpha, leads to a selective inhibition of protein synthesis. PKR also phosphorylates IkB, freeing NFkB to tranlocate to the nucleus and induce transcription of a number of gene products. PKR-induced apoptosis has recently been reported to be co-dependent on both the eIF2alpha and NFKB pathways in HeLa cells. Breast cancer was utilized as a model system to determine the role of PKR in loss of hormone and growth factor dependence in human cancers, as it appears inactive or hypoactive, as determined by eIF-2alpha phosphyorylation in this system. We hypothesized that hormone deprivation induces apoptosis in dependent cell lines through a PKR: NFKB mediated process, but this pathway is abrogated in hormone-independent cell lines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2003
- Accession Number
- ADA426882
Entities
People
- George K. Haines
Organizations
- Northwestern University