The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis.
Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.
Xing
X
X
The University of Texas M.D. Anderson Cancer Center, Department of Cancer Biology, Section of Molecular Cell Biology, Houston, Texas 77030, USA.
Wang
S C
SC
Xia
W
W
Zou
Y
Y
Shao
R
R
Kwong
K Y
KY
Yu
Z
Z
Zhang
S
S
Miller
S
S
Huang
L
L
Hung
M C
MC
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D017931:DNA Primers; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C065788:transcription factor PEA3