Role of elF-2a-Specific Protein Kinase (PKR) in the Proliferation of BreastCarcinoma Cells

摘要

The elF2a-specific protein kinase, PkR, has been implicated as a tumor suppressorgene because of its growth suppressive and translational inhibitory properties, as well as the ability of nonfunctional mutants of PKR to transform cells. We have sought to investigate the possibility that the aberrant regulation 6f cellular protein synthesis underlies the loss of growth control in breast carcinoma cells through dysfunction of the dsRNA activated, elF2a-specific protein kinase, PKR. We have compared the expression and regulation of activity of PKR in normal breast and breast carcinoma cell lines and found unusually high levels of PKR, as well as evidence of an inhibitor of PkR activity in breast carcinoma cells. This PKR inhibitor could be involved in the establishment of the transformed state of breast carcinoma cells and could also be responsible for the resistance of breast carcinoma cells to interferon treatment. These data represent the first documentation of a defect in PKR associated with a human malignancy.