Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN).

TY - JOUR

T1 - Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN).

AU - Hambek, Markus

AU - Baghi, Mehran

AU - Baumaun, Helena

AU - Strebhardt, Klaus

AU - Strebhard, Klaus

AU - Adunka, Oliver

AU - Gstöttner, Wolfgang

AU - Knecht, Rainald

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 25

SP - 1871

EP - 1875

JO - ANTICANCER RES

JF - ANTICANCER RES

SN - 0250-7005

IS - 3

M1 - 3

ER -