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Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons

Oncogene volume 23, pages 1693–1703 (2004)Cite this article

Abstract

Protein expression and de novo synthesis in normal and prostate cancer cell lines derived from the same patient were compared by proteomic analysis, and the effects of INFα and INFγ (INF=interferon) determined. The expressions of several INF-inducible proteins, including MxA, Nmi, PA28a and IFP53, were downregulated in the cancer cells. INFγ induced a more than twofold increase or decrease in the synthesis rates of almost twice as many proteins in the cancer cell line. The positive regulator of INF-induced transcription ISGF3γ was upregulated in the cancer cells and inversely regulated by INFα and INFγ in the normal and cancer cells. Moreover, ISGF3γ's induction by INFγ in the cancer cells was more enhanced by simultaneous stimulation with EGF, than its induction in the normal cells. In all, 31 differentially regulated proteins were identified by mass spectrometry analysis, several of which are involved in chaperone-assisted protein folding in the endoplasmic reticulum (ER) or in regulated protein degradation. Our results suggest that the exclusion of proteins by the ER quality control system, crosstalk between the EGF- and INF-induced signalling pathways and the regulation of INF-inducible genes are all altered in the prostate cancer cells. The combination of upregulated activity in the growth-promoting PI3K/Akt pathway, suppression of Nmi and overexpression of hnRNP-K and c-myc proteins may explain why the prostate cancer cells were found to be more resistant to the growth inhibitory effects of INFγ.

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Acknowledgements

We thank Dr Suzanne L Topalian for providing us with the prostate cell lines 1542-NP2TX and 1542-CP3TX, Dr Warren Leonard for the kind provision of α-Nmi rabbit polyclonal antibody, Dr Manfred Schwab for providing GFP-tagged Nmi cDNA, Dr Gideon Dreyfuss for providing α-hnRNP-K mouse monoclonal antibody and Dr Otto Haller for providing α-MxA antibody and Flag-tagged MxA cDNA.

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  1. Kohji Nagano

    Present address: Department of Proteomics Research, Institute of Medical Sciences, University of Tokyo, Japan

Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Royal Free and University College London Medical School, London, UK

    Kohji Nagano, Akunna Akpan, Alice Yang, Steve Corless, Chris Wood, Claire Hastie, Marketa Zvelebil, Rainer Cramer & Soren Naaby-Hansen

  2. Prostate Cancer Research Center, Royal Free and University College London Medical School, London, UK

    John R Masters

  3. Department of Biochemistry and Molecular Biology, University College London, London, UK

    Marketa Zvelebil, Rainer Cramer & Soren Naaby-Hansen

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Correspondence to Soren Naaby-Hansen.

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Nagano, K., Masters, J., Akpan, A. et al. Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons. Oncogene 23, 1693–1703 (2004). https://doi.org/10.1038/sj.onc.1207297

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