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„Transforming growth factor β“ im Prostatakarzinom

Zelluläre Wirkungen und molekulare Grundlagen

Transforming growth factor β in prostate cancer

Cellular effects and basic molecular mechanisms

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Zusammenfassung

Der pleiotrope Wachstumsfaktor „transforming growth factor β“ (TGF-β) ist in diverse Signalwege involviert und kann eine Vielzahl von Zellantworten beeinflussen. Bei Entstehung und Karzinogenese des Prostatakarzinoms (PCa) können dies sowohl antionkogene Mechanismen (Wachstumshemmung, Apoptose) als auch proonkogene Prozesse sein (Proliferation, Zellbeweglichkeit, Modulierung der Tumorumgebung). Die ursprünglich antiproliferative Wirkung von TGF-β wird dabei im Verlauf der Tumorprogression immer mehr von proonkogenen Effekten überlagert, die häufig durch die Interaktion mit proliferativen Signalkaskaden wie „Mitogen-activated protein-kinase-“ (MAP-Kinase-) oder Androgenrezeptor- (AR-)Signalwegen vermittelt werden. Obgleich TGF-β ein wichtiger Modulator der PCa-Progression ist, sind die zugrundeliegenden molekular-pathologischen Prozesse bisher nur unvollständig verstanden.

Abstract

The multifunctional cytokine transforming growth factor β (TGFβ) plays a dual role in prostate cancer (PCa), cell growth and tumorigenesis, reflected by its opposing properties of anti-oncogenic (e.g. growth inhibition and apoptosis) and pro-oncogenic effects (e.g. proliferation, cell motility and remodelling of the microenvironment). In the later stages of PCa, TGFβ loses anti-proliferative and thereby tumor-suppressive functions and shifts to a tumorigenic phenotype, mainly initiated by cross-talk between TGFβ signalling and other proliferation signal transduction pathways, such as mitogen-activated protein kinase (MAPK) and androgen receptor (AR) signalling. Although TGFβ plays an important role in tumor progression little is known about the underlying effects of TGFβ in the molecular pathology of PCa.

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Abb. 1

Abbreviations

PCa:

Prostatakarzinom

TGF-β:

„Transforming growth factor“ β

BMP:

„Bone morphogenetic protein“

LAP:

„Latency associated protein“

LTBP:

„Latent TGF-β binding protein“

TβRI/II/III:

TGF-β-Rezeptor Typ I/II/III

Smad:

Homolog der Proteine SMA und MAD

EZM:

Extrazelluläre Matrix

EMT:

Epithelial-zu-mesenchymal-Transition

PKA:

Proteinkinase A

MAPK:

„Mitogen-activated protein kinase“

MEK MAPK:

„MAP Kinases Kinases Kinase“

MEKK MEK:

„MAP Kinases Kinases Kinases Kinase“

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Authors and Affiliations

  1. Klinik und Poliklinik für Urologie, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Deutschland

    M.B. Stope, C. Rönnau, T. Schubert, D. Staar, J. Bradl, A. Streitbörger, N. Kroeger, U. Zimmermann & M. Burchardt

  2. Institut für Medizinische Biochemie und Molekularbiologie, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Deutschland

    T. Schubert, D. Staar, J. Bradl, A. Streitbörger & R. Walther

  3. Klinik für Onkologie, Hämatologie und Stammzelltransplantation, Universitätsklinikum Aachen, RWTH Aachen, Aachen, Deutschland

    P. Ziegler

  4. Klinik für Urologie, onkologische Urologie und Kinderurologie, Krankenhaus Düren gem. GmbH, Düren, Deutschland

    C. Börgermann

Authors
  1. M.B. Stope
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  2. C. Rönnau
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  3. T. Schubert
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  4. D. Staar
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  5. J. Bradl
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  6. P. Ziegler
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  7. A. Streitbörger
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  8. N. Kroeger
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  9. U. Zimmermann
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  10. R. Walther
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  11. M. Burchardt
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  12. C. Börgermann
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Correspondence to M.B. Stope.

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Stope, M., Rönnau, C., Schubert, T. et al. „Transforming growth factor β“ im Prostatakarzinom. Urologe 52, 378–383 (2013). https://doi.org/10.1007/s00120-012-3049-5

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  • DOI: https://doi.org/10.1007/s00120-012-3049-5

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