Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2

• DOI: 10.1016/j.ccr.2004.07.012
• Publication Date: 2004-09-21T18:24:42Z
• Authors: Shao-Chun Wang; Huang-Chun Lien; Weiya Xia; I.-Fen Chen; Hui-Wen Lo; Zhiqin Wang; Mohamed Ali-Seyed; Dung-Fang Lee; Geoffrey Bartholo...; Fu Ou-Yang; Dipak K. Giri; Mien-Chie Hung
• Keywords: ErbB

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.