Article (Scientific journals)
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
Vernimmen, Douglas; Begon, Dominique; Salvador, Christophe et al.
2003In Biochemical Journal, 370 (Pt 1), p. 323-329
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Keywords :
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
Abstract :
[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.
Research center :
Giga-Cancer - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vernimmen, Douglas;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire
Begon, Dominique ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire
Salvador, Christophe;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire
Gofflot, Stéphanie ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire
Grooteclaes, Madeleine;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire
Winkler, Rose ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire
Language :
English
Title :
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
Alternative titles :
[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
Publication date :
15 February 2003
Journal title :
Biochemical Journal
ISSN :
0264-6021
eISSN :
1470-8728
Publisher :
Portland Press, London, United Kingdom
Volume :
370
Issue :
Pt 1
Pages :
323-329
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Fonds Léon Fredericq [BE]
Fédération Belge contre le Cancer
CAC - Centre anticancéreux près l'Université de Liège asbl [BE]
Télévie [BE]
Commentary :
The final version of record is available at http://www.biochemj.org/bj/370/0323/bj3700323.htm
Available on ORBi :
since 15 January 2009

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