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Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR

Oncogene volume 21, pages 8741–8748 (2002)Cite this article

Abstract

The interferon-inducible, double-stranded RNA (dsRNA)-activated protein kinase, PKR, plays key roles in regulation of cell growth and differentiation, and has been postulated as a tumor suppressor. Downstream effectors of PKR include the translation initiation factor, eIF2α, and the transcription factor, NF-κB. We found elevated levels of PKR protein, dsRNA-dependent PKR autophosphorylation activity, and phosphorylated eIF2α in melanoma cells compared to nontransformed melanocytes in culture. Treatment with interferon-α2b further induced PKR expression and activity. Immunohistochemical analysis of primary melanomas demonstrated minimal PKR immunoreactivity, but melanoma lymph node metastases expressed a high level of PKR protein. Furthermore, analysis of colon cancer specimens revealed that transformation from normal mucosa to adenomas and carcinomas was coincident with an increase in PKR expression. These data do not support the concept of PKR as a classic tumor suppressor but instead suggest that PKR upregulation occurs at defined steps in cancer progression, probably as a cellular response to neoplasia.

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Acknowledgements

We wish to thank Gene Marquet for valuable technical assistance with the immunohistochemistry. This work was supported by grant AI34552 to MBM from the National Institute of Health.

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Authors and Affiliations

  1. Department of Surgery, New Jersey Medical School/University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, 07103, New Jersey, NJ, USA

    Steve H Kim

  2. Surgical Services, VA New Jersey Healthcare System, 385 Tremont Avenue, East Orange, 07018, New Jersey, NJ, USA

    Steve H Kim

  3. Department of Biochemistry and Molecular Biology, New Jersey Medical School/University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, 07103, New Jersey, NJ, USA

    Shobha Gunnery & Michael B Mathews

  4. Pathology and Laboratory Medicine Services, VA New Jersey Healthcare System, 385 Tremont Avenue, East Orange, 07018, New Jersey, NJ, USA

    Jin K Choe

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Correspondence to Steve H Kim.

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Kim, S., Gunnery, S., Choe, J. et al. Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR. Oncogene 21, 8741–8748 (2002). https://doi.org/10.1038/sj.onc.1205987

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