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

Wang S.C., Lien H.C., Xia W., Chen I.F., Lo H.W., Wang Z., Ali-Seyed M., Lee D.F., Bartholomeusz G., Ou-Yang F., Giri D.K., Hung M.C.

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.

Cancer Cell 6:251-261(2004) [PubMed] [Europe PMC]