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  • Original Paper
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Human breast cancer cells contain elevated levels and activity of the protein kinase, PKR

Oncogene volume 19, pages 3086–3094 (2000)Cite this article

Abstract

PKR is a double-stranded (ds) RNA activated protein kinase whose expression is induced by interferon. Activated PKR phosphorylates its cellular substrate, eIF2, an essential initiation factor of translation. Prior evidence from a murine model system suggested that PKR may act as a tumor suppressor, but the evidence from human tumors is equivocal. To study PKR function in human breast cancer, PKR activity was measured in mammary carcinoma cell lines and nontransformed mammary epithelial cell lines. If PKR functioned as a tumor suppressor in this system, its activity would be higher in nontransformed cells than in carcinoma cells. On the contrary, PKR autophosphorylation and the phosphorylation of its substrate, the α-subunit of eIF2, is 7–40-fold higher in lysates prepared from breast carcinoma cell lines than in those from nontransformed epithelial cell lines. Correspondingly, a larger proportion of eIF2α is present in a phosphorylated state in carcinoma cell lines than in nontransformed cell lines. Protein synthesis is not inhibited by the high eIF2α phosphorylation in carcinoma cells, probably because they contain higher levels of eIF2B, the initiation factor that is inhibited by eIF2α phosphorylation. The dramatically lower PKR activity in nontransformed cell lines is partially due to lower PKR protein levels (2–4-fold) as well as to the presence of a PKR inhibitor. The nontransformed cells contain P58, a known cellular inhibitor of PKR that physically interacts with PKR and may be responsible for the low PKR activity in these cells. Taken together, these observations call into question the role of PKR as a tumor suppressor and suggest a positive regulatory role of PKR in growth control of breast cancer cells.

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Acknowledgements

This work was supported by seed grant from the Dean's Biomedical Research Fund RA3467 and by NIH grant AI34552. We would like to thank R Wieder, M Clemens, JWB Hershey, M Katze and C Proud for cell lines and other essential reagents.

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  1. Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, 185, South Orange Avenue, Newark, 07103, New Jersey, NJ, USA

    Steve H Kim, Adam P Forman, Michael B Mathews & Shobha Gunnery

  2. Department of Surgery, New Jersey Medical School, UMDNJ, 185, South Orange Avenue, Newark, 07103, New Jersey, NJ, USA

    Steve H Kim

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Kim, S., Forman, A., Mathews, M. et al. Human breast cancer cells contain elevated levels and activity of the protein kinase, PKR. Oncogene 19, 3086–3094 (2000). https://doi.org/10.1038/sj.onc.1203632

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