Diversity of epidermal growth factor receptor-mediated activation of downstream molecules in human lung carcinomas

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Shioto SuzukiYoh Dobashi

Abstract

The correlations among epidermal growth factor receptor (EGFR) gene amplification, gene mutation, overexpression/phosphorylation of EGFR protein and activation of its downstream molecules, signal transducers and activators of transcription 3 (Stat-3), Akt and extracellular signal-related protein kinase 1/2 (Erk1/2) were investigated in 28 cases of human lung carcinomas. In five cases of carcinomas with EGFR amplification, EGFR expression and phosphorylation levels were higher than other cases, and Stat-3 was activated in all five cases. Point mutations in the tyrosine kinase domain of EGFR were detected in five cases, one of which was also associated with gene amplification. In these five cases, both EGFR expression and phosphorylation were enhanced, and Akt was activated in four cases. In the remaining 19 cases, EGFR protein expression was upregulated in eight cases and phosphorylated in four cases, but neither EGFR nor phosphorylated-EGFR expression levels specifically correlated with activation of particular downstream molecules. In general, either Stat-3 or Akt, but not both, was activated reciprocally and complementarily to each other, as indicated by their phosphorylation. However, Erk1/2 was activated regardless of the s...Continue Reading

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Citations

Aug 4, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yoh DobashiAkishi Ooi
May 1, 2007·Expert Opinion on Therapeutic Targets·Jen Jen Yeh, Channing J Der
Feb 3, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Shinobu HosokawaKatsuyuki Kiura
Dec 18, 2009·Journal of Cellular and Molecular Medicine·Luis Paz-AresBarbara Klughammer
Jul 26, 2012·Virchows Archiv : an International Journal of Pathology·Shioto SuzukiAkishi Ooi
Mar 23, 2018·International Journal of Clinical Oncology·Akira NishikadoYoshinobu Hirose

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