title: Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN).
abstract: Proliferation of squamous cell carcinoma of the head and neck (SCCHN) depends on epidermal growth factor receptor (EGFR) expression. The EGFR activates different signal pathways leading to gene transcription in the nucleus due to cell cycle progression and proliferation of tumor cells. AKT, STAT3 and MAPK play central roles in these pathways. However, they are not only regulated by the EGFR. We therefore investigated whether a specific inhibitor of the EGFR tyrosine kinase (ZD 1839 or Iressa) is able to inhibit phosphorylation of these three signals at the same time. Western blot analysis of pretreated SCCHN cells revealed that ZD 1839 greatly reduces the amount of phosphorylated AKT, STAT3 as well as MAPK Surprisingly, this effect was not dose-dependent between the concentration range of 5.15 to 41.2 microM/ml. We conclude that Iressa has a high potency to inhibit nuclear gene transcription responsible for cell cycle progression. Furthermore, dose reduction of Iressa in the case of toxicity may not severely influence the response to treatment.
authors.affiliation: Department of Otorhinolaryngology, School of Medicine, J. W. Goethe University, 60590 Frankfurt, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hambek
authors.forename: Mehran
authors.initials: M
authors.lastname: Baghi
authors.forename: Helena
authors.initials: H
authors.lastname: Baumaun
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebhardt
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebhard
authors.forename: Oliver
authors.initials: O
authors.lastname: Adunka
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gstöttner
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D000077156:Gefitinib