Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2.
Pathological expression of human ErbB-2 protein, also known as HER-2, is common in many types of cancer. ErbB-2 is a member of the EGF receptor tyrosine kinase family and has been rigorously studied as a signaling molecule on the cell membrane. Here, we report that ErbB-2 is also expressed in the nucleus in cultured cells as well as primary tumor tissues. Nuclear ErbB-2 was found to associate with multiple genomic targets in vivo, including the cyclooxygenase enzyme COX-2 gene promoter. ErbB-2 forms a complex at a specific nucleotide sequence of the COX-2 promoter and is able to stimulate its transcription. This study demonstrates the presence of ErbB-2 in the nucleus and identifies the function of ErbB-2 as a transcriptional regulator.
Wang
Shao-Chun
SC
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Lien
Huang-Chun
HC
Xia
Weiya
W
Chen
I-Fen
IF
Lo
Hui-Wen
HW
Wang
Zhiqin
Z
Ali-Seyed
Mohamed
M
Lee
Dung-Fang
DF
Bartholomeusz
Geoffrey
G
Ou-Yang
Fu
F
Giri
Dipak K
DK
Hung
Mien-Chie
MC
D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; C496540:PTGS2 protein, human