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Phosphoinositid-3-Kinase- (PI3-K) Expression

Tumorgenese von Plattenepithelkarzinomen der Mundhöhle

  • Schwerpunkt: Orale Pathologie/Pathologien der Speicheldrüsen—Originalarbeit
  • Published:
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Zusammenfassung

Phospoinositid-3-Kinase (PI3-K) ist ein heterodimeres Enzym und in die Regulation von Zellzyklus, Apoptose, Zelladhäsion und Zellmotilität eingebunden. Es wird als Proto-Onkogen in humanen Karzinomen diskutiert. In der vorliegenden Arbeit wurde die PI3-K-Expression in normalem Plattenepithel der Mundhöhle, Dysplasien, Carcinomata in situ, invasiven Karzinomen und Lymphknotenmetastasen immunhistologisch untersucht. Die stärkste Immunreaktivität für die regulatorische p85α- und die katalytische p110α-Untereinheit wurde in invasiven Tumoren und Metastasen gefunden. Carcinomata in situ zeigten eine herdförmige Reaktion, Dysplasien und normales Epithel reagierten überwiegend negativ. Zusätzlich hemmte der PI3-K-Inhibitor LY294002 die Proliferations- und Invasionsfähigkeit der humanen HNSCC-Zelllinie CAL-27 und induzierte die Apoptose in vitro.

Unsere Ergebnisse deuten darauf hin, dass PI3-K ein Malignitäts- und Invasionsmarker beim Plattenepithelkarzinom des oberen Aerodigestivtraktes (HNSCC) ist. Wir schlagen vor, PI3-K als Proto-Onkogen in das vorläufige Mehrschrittkanzerogenesemodell des HNSCC aufzunehmen. PI3-K ist darüber hinaus ein potenzielles Ziel pharmakologischer Intervention.

Abstract

Phosphoinositide 3-kinase (PI3-K) is a heterodimeric enzyme involved in the regulation of mitogenesis, apoptosis, cell adhesion, and motility. PI3-K was suggested as a protooncogene in human cancer. To determine the expression of PI3-K during cancerogenesis and tumor invasion of HNSCC, we investigated normal and dysplastic epithelium of the oral cavity, squamous cell carcinoma and lymph node metastasis by immunohistochemistry. The strongest immunoreactivity for p85α and p110α was found in invasive tumors and their metastases. Carcinomas in situ showed a focal positivity. Dysplasias and normal epithelium reacted predominantly negatively. The PI3-K inhibitor LY294002 inhibited proliferation and invasion of the HNSCC cell line CAL-27 and induced apoptosis in vitro.

Our data suggest PI3-K as a marker of malignancy and tumor invasion. We suggest including PI3-K in the multistep carcinogenesis model of HNSCC. In addition, PI3-K is a potential target for pharmacological intervention.

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Authors and Affiliations

  1. Institut für Pathologie, Justus-Liebig-Universität Gießen

    U. Stahl, J. Wenk, F. Wagener, J. Woenckhaus, U. Gamerdinger, A. Battmann & T. Dreyer

  2. Institut für Pathologie, Justus-Liebig-Universität Gießen, Langhansstraße 10, 35385 , Gießen

    U. Stahl

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  1. U. Stahl
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  2. J. Wenk
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  3. F. Wagener
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Correspondence to U. Stahl.

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Stahl, U., Wenk, J., Wagener, F. et al. Phosphoinositid-3-Kinase- (PI3-K) Expression. Pathologe 25, 31–37 (2004). https://doi.org/10.1007/s00292-003-0673-2

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  • DOI: https://doi.org/10.1007/s00292-003-0673-2

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