title: Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Wang
authors.forename: Huang-Chun
authors.initials: HC
authors.lastname: Lien
authors.forename: Weiya
authors.initials: W
authors.lastname: Xia
authors.forename: I-Fen
authors.initials: IF
authors.lastname: Chen
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Lo
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Wang
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ali-Seyed
authors.forename: Dung-Fang
authors.initials: DF
authors.lastname: Lee
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bartholomeusz
authors.forename: Fu
authors.initials: F
authors.lastname: Ou-Yang
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Giri
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: 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
chemical_list: 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