TIEG1 inhibits breast cancer invasion and metastasis by inhibition of epidermal growth factor receptor (EGFR) transcription and the EGFR signaling pathway.
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.
Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China.
Wei
W
Jin
Bo-bin
BB
Chen
Ji-yu
JY
Li
Hua
H
Zhu
Mark
M
Huang
Sheng-mei
SM
Gu
Qiao-qiao
QQ
Wang
Jia-ying
JY
Chen
Sanjian
S
Yu
Jiong
J
Wu
Zhi-ming
ZM
Shao
D000107:Acetylation; D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D051765:Early Growth Response Transcription Factors / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D015398:Signal Transduction
D051765:Early Growth Response Transcription Factors; D006657:Histones; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D066246:ErbB Receptors