Langenbecks Archiv für Chirurgie

, Volume 380, Issue 2, pp 96–101 | Cite as

Wachstum und invasion beim differenzierten schilddrüsenkarzinom: stellenwert der signaltransduktion

  • Th. Hölting
  • O. Y. Duh
  • O. H. Clark
  • Ch. Herfarth
Originalarbeit
Received:

Zusammenfassung

Der Stellenwert der Signaltransduktionssysteme Adenylatzyklase, Proteinkinase C (PKC) und Tyrosinkinase für Wachstum und Invasion einer follikulären (FTC 133) und einer papillären Schilddrüsenkarzinomzellinie (PTC-UC1) wurde analysiert. Agonisten und Antagonisten von cAMP waren ohne Effekt. Der PKC-Agonist TPA stimulierte Wachstum und Invasion von FTC133 um jeweils 15%, wohingegen der PKC-Antagonist Staurosporin Wachstum und Invasion von FTC 133 um 47 bzw. 32% hemmte. Staurosporin neutralisierte den stimulierenden Effekt von Thyreotropin (TSH), nicht aber von Epidermal growth factor (EGF). Der stimulierende Effekt von EGF auf Wachstum und Invasion beider Zellinien wurde durch einen monoklonalen Antikörper gegen den EGF-Rezeptor neutralisiert. Der Tyrosinkinaseantagonist Genistein hob die EGF-, nicht aber die TSH-Stimulation auf. Pertussistoxin hemmte Zellwachstum (FTC 133: 22%) und -invasion (FTC133: 18%). Choleratoxin hatte einen weniger inhibierenden Effekt. Die Signaltransduktion von Wachstum und Invasion differenzierter Schilddrüsenkarzinome in vitro ist komplex und wird nicht allein von der Adenylatzyklase kontrolliert.

Growth and invasion in differentiated thyroid cancer: relative value of signal transduction

Abstract

We investigated the role of three different signal transduction systems adenylate-cyclase (AC), protein kinase C (PKC) and tyrosine kinase (TK) for growth and invasion of a human follicular (FTC 133) and a human papillary thyroid cancer cell line (PTC-UCI). Cyclic AMP stimulators and inhibitors had no effect at any concentration. The PKC agonist TPA enhanced both growth and invasion of FTC133 by 15%, whereas staurosporine, a PKC antagonist, inhibited growth by 47% and invasion by 32%. The latter also reversed thyrotropin (TSH) stimulation, but not epidermal growth factor (EFG) stimulation. EGF-stimulated growth and invasion of both cell lines were abolished by EGF-receptor antagonism using a monoclonal antibody. The tyrosine kinase antagonist genistein reversed EGF, but not TSH, stimulation. Pertussis toxin inhibited growth (FTC133: 22%) and invasion (FTC133: 18%). Cholera toxin was less inhibitory. Obviously, signal transduction of differentiated thyroid cancer is complex and systems other than adenylate cyclase are crucial for basal invasion and growth of follicular thyroid cancer cells in culture.

Key words

Differentiated thyroid cancer Invasion Signal transduction 
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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Th. Hölting
    • 1
  • O. Y. Duh
    • 2
  • O. H. Clark
    • 2
  • Ch. Herfarth
    • 1
  1. 1.Chirurgische UniversitätsklinikHeidelberg
  2. 2.Chirurgische AbteilungMount Zion Hospital/UCSFSan FranciscoUSA

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