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Altered levels of Smad2 and Smad4 are associated with human prostate carcinogenesis

Prostate Cancer and Prostatic Diseases volume 9, pages 185–189 (2006)Cite this article

Abstract

Alterations have been demonstrated in ligand and cognate receptor system of the transforming growth factor beta (TGF-β) pathway in prostate cancer (PC). Still, little is known about changes in the activity of the intracellular Smad cascade of TGF-β signaling during prostate carcinogenesis. We used immunohistochemistry to analyze phosphorylated Smad2 (p-Smad2), nuclear Smad4 and inhibitory-Smad7 in epithelial cells of normal, hyperplastic and malignant prostate. Specimens comprised 49 tissue cores of PC, 10 benign prostate hypertrophies and three normal prostates. Nuclear p-Smad2 (P<0.001) and nuclear Smad4 (P=0.023) were significantly decreased in PC with remarkable variations in cytoplasmic Smad7 levels. Substantial decreases in p-Smad2 and Smad4 levels were found in specimens with primary Gleason grades 3 and 4, whereas in grade 5, levels were markedly higher. Our results provide the first evidence for changes and reversible attenuation in the Smad system of the TGF-β pathway during prostate carcinogenesis.

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Acknowledgements

We thank Marianne Kuuslahti and Tiina Keisala for their skillful technical assistance. This study was supported by grants from the Medical Research Fund of Tampere University Hospital the Finnish Cancer Foundation and the Finnish Academy.

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Authors and Affiliations

  1. Department of Anatomy, Medical School, University of Tampere, Tampere, Finland

    M C Perttu & H Syvälä

  2. Department of Pathology, Medical School and Tampere University Hospital, University of Tampere, Tampere, Finland

    P M Martikainen

  3. School of Public Health, University of Tampere, Tampere, Finland

    H S A Huhtala

  4. Department of Cell Biology, Medical School, University of Tampere, Tampere, Finland

    M Bläuer

  5. Department of Urology, Medical School and Tampere University Hospital, University of Tampere, Tampere, Finland

    T L J Tammela

  6. Department of Anatomy and Department of Clinical Chemistry, Medical School and Tampere University Hospital, University of Tampere, Tampere, Finland

    P J Tuohimaa

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  1. M C Perttu
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Correspondence to M C Perttu.

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Perttu, M., Martikainen, P., Huhtala, H. et al. Altered levels of Smad2 and Smad4 are associated with human prostate carcinogenesis. Prostate Cancer Prostatic Dis 9, 185–189 (2006). https://doi.org/10.1038/sj.pcan.4500871

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  • DOI: https://doi.org/10.1038/sj.pcan.4500871

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