Reference : Identification of HTF (HER2 transcription factor) as an AP-2 (activator protein-2) tr...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/4230
Identification of HTF (HER2 transcription factor) as an AP-2 (activator protein-2) transcription factor and contribution of the HTF binding site to ERBB2 gene overexpression
English
[fr] Identification de HTF (facteur de transcription HER2) en tant que facteur de transcription AP-2 (protéine activatrice-2) et contribution du site de liaison HTF à la surexpression du gène ERBB2
Vernimmen, Douglas [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
Begon, Dominique [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > > >]
Salvador, Christophe [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
Gofflot, Stéphanie mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
Grooteclaes, Madeleine [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
Winkler, Rose mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > > >]
15-Feb-2003
Biochemical Journal
Portland Press
370
Pt 1
323-329
Yes (verified by ORBi)
International
0264-6021
London
England
[en] AP-2 binding site ; ERBB2 promoter ; HER2 transcription factor ; HTF ; human ; transcription regulation ; transfection ; BT-474 ; luciferase ; EMSA ; DNase I footprint ; Mutagenesis, Site-Directed ; Tumor Cells, Cultured ; Western blotting ; oncogene
[en] The ERBB2 gene is overexpressed in 30% of human breast cancers and this is correlated with poor prognosis. Overexpression of the ERBB2 gene is due to increased transcription and gene amplification. Our previous studies have identified a new cis element in the ERBB2 promoter which is involved in the gene's overexpression. This cis element, located 501 bp upstream from the main ERBB2 transcription initiation site, binds a transcription factor called HTF (HER2 transcription factor). We report here the identification of HTF as an AP-2 (activator protein-2) transcription factor. The new cis element is bound by AP-2 with high affinity, compared with a previously described AP-2 binding site located 284 bp downstream. Co-transfection of an AP-2alpha expression vector with a reporter vector containing the newly identified AP-2 binding site in front of a minimal ERBB2 promoter induced a dose-dependent increase in transcriptional activity. We examined the contribution of the new AP-2 binding site to ERBB2 overexpression. For this purpose we abolished the new and/or the previously described AP-2 binding sequence by site-directed mutagenesis. The results show that the two functional AP-2 sites in the first 700 bp of the ERBB2 promoter co-operate to achieve maximal transcriptional activity.
Giga-Cancer
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Fonds Léon Fredericq (Liège, Belgique) ; Fédération Belge contre le Cancer ; Centre Anticancéreux attaché à l'Université de Liège ; Télévie (Belgique)
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/4230
10.1042/BJ20021238
http://www.biochemj.org/bj/370/0323/bj3700323.htm
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12418962
The final version of record is available at http://www.biochemj.org/bj/370/0323/bj3700323.htm

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