Role of elF-2alpha-Specific Protein Kinase (PKR) in the Proliferation of Breast Carcinoma Cells.
Abstract
Levels of the elF-2a-specific protein kinase, PkR, are higher in several breast carcinoma cell lines including the estrogen-responsive cell lines, MOF-7 and T-47D, as well as estrogen- independent cell lines, BT-20 and MDA-MB-468, compared with the normal breast cell line, Hs578 Bst, or the human HeLa cell line. In contrast, the phosphorylation state of elF-2a is very low in the breast carcinoma cell lines compared to the normal human breast cell line Hs578 Bst and HeLa cells, even at high cell densities, suggesting an inhibition of PkR activity in the breast oarninoma cell lines. In support of this hypothesis, treatment of cells with either alpha- or Beta-interferon, although increasing PKR levels slightly, do not result in higher steady state levels of elF-2a phosphorylation. These results suggest that deregulation of PKR activity is occurring at some level in breast carcinoma cell lines. This deregulation could result from increased levels/activities of cellular PKR inhibitory proteins, or from inactivating mutations in the PKR gene. These results are consistent with the putative role of PKR as a tumor suppressor gene and in accordance with the idea that activation of the translational machinery may be one mechanism through which oncogenes exert their transforming function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 29, 1995
- Accession Number
- ADA299499
Entities
People
- Rosemary Jagus
Organizations
- University of Maryland