Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas

Donald Johnston, Harry Hall, Teresa P. DiLorenzo, Bettie M. Steinberg

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Laryngeal papillomas are benign tumors caused by human papillomaviruses types 6 and 11. This study addressed alterations in levels of signal transduction from the epidermal growth factor receptor (EGFR) in papillomas and cultured papilloma cells compared to normal tissue and cells. Mitogen- activated protein kinase (MAPK) was activated to a greater extent, phosphotyrosine was more abundant, and EGFR was overexpressed in laryngeal papillomas compared to normal laryngeal epithelium by Western blot analysis. The EGFR was 3 times more abundant in cultured papilloma cells than in normal laryngeal cells by Scatchard analysis and Western blot, without gene amplification or an increase in steady-state levels of mRNA. Following stimulation with EGF, a significant portion of the EGFR was recycled to the surface in papilloma cells, whereas in normal cells, it was not. Tyrosine kinase activity and activation of MAPK was more responsive to epidermal growth factor stimulation in papilloma cells than in uninfected primary laryngeal cells. PD153035, a specific inhibitor of the EGFR, and an EGFR- specific antibody that blocks ligand binding completely abrogated basal MAPK activation by endogenous ligands in laryngeal papilloma cells. These results demonstrated that infection of laryngeal epithelium by low-risk human papillomaviruses elevates the EGFR by posttranslational mechanisms, increasing its responsiveness to ligand-mediated activation. They also showed that MAPK activation in laryngeal papillomas depends upon ligand-mediated EGFR stimulation.

Original languageEnglish (US)
Pages (from-to)968-974
Number of pages7
JournalCancer Research
Volume59
Issue number4
StatePublished - Feb 15 1999

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Papilloma
Epidermal Growth Factor Receptor
Mitogen-Activated Protein Kinases
Laryngeal Mucosa
Ligands
Epidermal Growth Factor
Cultured Cells
Western Blotting
Human papillomavirus 11
Human papillomavirus 6
Phosphotyrosine
Gene Amplification
Protein-Tyrosine Kinases
Signal Transduction
Messenger RNA
Antibodies
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas. / Johnston, Donald; Hall, Harry; DiLorenzo, Teresa P.; Steinberg, Bettie M.

In: Cancer Research, Vol. 59, No. 4, 15.02.1999, p. 968-974.

Research output: Contribution to journalArticle

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