Epidermal growth factor increased the expression of alpha2beta1-integrin and modulated integrin-mediated signaling in human cervical adenocarcinoma cells.
Epidermal growth factor (EGF) receptor (EGFR) is involved in various basic biochemical pathways and is thus thought to play an important role in cell migration. We examined the effect of EGF on motility, migration, and morphology of a human adenocarcinoma cell line CAC-1. EGF treatment increased the motility of cervical adenocarcinoma cells and promoted migration of the cells on fibronectin and type IV collagen. EGF induced morphological changes with lamellipodia during EGFR-mediated motility. The results of an immunoprecipitation study showed that EGF up-regulated the expression of alpha2beta1-integrin in a dose-dependent manner. EGF-induced cell migration was blocked by alpha2beta1-integrin antibody. Our results also showed that EGF treatment stimulated the level of tyrosine dephosphorylation of FAK, which is required for EGF-induced changes in motility, migration, and cell morphology. A tyrosine kinase inhibitor (ZD1839) blocked EGF-induced changes in cervical adenocarcinoma cells. The results suggest that EGF promotes cell motility and migration and increases the expression of alpha2beta1-integrin, possibly by decreasing FAK phosphorylation.
Department of Obstetrics and Gynecology, Sapporo Medical University, School of Medicine, Sapporo, Japan. ikuhitoy@samed.ac.jp
Ikuhito
I
Yamanaka
Motoiki
M
Koizumi
Tsuyoshi
T
Baba
Satoko
S
Yamashita
Takahiro
T
Suzuki
Ryuichi
R
Kudo
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D024141:Collagen Type IV / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D024141:Collagen Type IV; D004791:Enzyme Inhibitors; D005353:Fibronectins; D038982:Integrin alpha2beta1; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human