Epidermal growth factor inhibits the growth of TE8 esophageal cancer cells through the activation of STAT1.
BACKGROUND
Epidermal growth factor receptors (EGFRs) mediate growth signals in a variety of normal and malignant cells. However, the issue of whether the EGF/EGFR system contributes to the progression of esophageal cancer cells remains controversial. The aim of the present study was to determine the role of EGFR in the growth of esophageal cancer cell lines.


METHODS
Three esophageal cancer cell lines, TE1, TE2, and TE8, were stimulated with EGF, and cellular growth was then evaluated by cell number. The activation of signal transducers and activators of transcription (STATs) and the expression of the cyclin-dependent kinase (CDK) inhibitor p21/WAF1 were determined by an electromobility shift assay and Northern blot analysis, respectively.


RESULTS
EGF inhibited the growth of TE8 cells, while no significant effects were observed for TE1 and TE2 cells. The treatment of TE8 cells with EGF induced the activation of STAT1 and STAT3, followed by the expression of p21/WAF1. The introduction of a dominant-negative STAT1 construct into TE8 cells abolished not only growth inhibition but also p21/WAF1 induction by EGF.


CONCLUSIONS
The findings herein suggest that EGF inhibits the growth of some esophageal cancer cells that overexpress EGFR and that the activation of STAT1 constitutes a critical event which is required for the inhibition of growth by EGF.
Ichiba
Makoto
M
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan.
Miyazaki
Yoshiji
Y
Kitamura
Shinji
S
Kiyohara
Tatsuya
T
Shinomura
Yasuhisa
Y
Matsuzawa
Yuji
Y
D015152:Blotting, Northern; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000473:pathology*; D006801:Humans; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D066246:ErbB Receptors