TIEG1 can induce apoptosis of cancer cells, but its role in inhibiting invasion 
and metastasis has not been reported and is unclear. In this study, we find that 
decreased TIEG1 expression is associated with increased human epidermal growth 
factor receptor (EGFR) expression in breast cancer tissues and cell lines. TIEG1 
plays an important role in suppressing transcription of EGFR by directly binding 
to the EGFR promoter. While overexpression of TIEG1 attenuates EGFR expression, 
knockdown of TIEG1 stimulates EGFR expression. Furthermore, TIEG1 and HDAC1 form 
a complex, which binds to Sp1 sites on the EGFR promoter and inhibits its 
transcription by suppressing histone acetylation. TIEG1 significantly inhibits 
breast cancer cell invasion, suppresses mammary tumorigenesis in xenografts in 
mice, and decreases lung metastasis by inhibition of EGFR gene transcription and 
the EGFR signaling pathway. Therefore, TIEG1 is an antimetastasis gene product; 
regulation of EGFR expression by TIEG1 may be part of an integral signaling 
pathway that determines and explains breast cancer invasion and metastasis.