Reference : Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mam...
Scientific journals : Article
Human health sciences : Oncology Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/4088
Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells.
English
[fr] YY1 coopère avec AP-2 pour stimuler l'expression du gène ERBB2 dans les cellules de cancer du sein
Begon, Dominique[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
Delacroix, Laurence[Université de Liège - ULg > Département des sciences cliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
Vernimmen, Douglas[University of Oxford > Institute of Molecular Medecine, John Radcliffe Hospital > Medical Research Council Molecular Haematology Unit > >]
Jackers, Pascale[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
Winkler, Rose[Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Laboratoire d'Oncologie Moléculaire > >]
[en] Overexpression of the ERBB2 oncogene is observed in about 30% of breast cancers and is generally correlated with a poor prognosis. Previous results from our and other laboratories indicated that elevated transcriptional activity contributes significantly to the overexpression of ERBB2 mRNA in mammary adenocarcinoma cell lines. Activator protein 2 (AP-2) transcription factors account for this overexpression through two recognition sequences located 215 and 500 bp upstream from the transcription start site. Furthermore, AP-2 transcription factors are highly expressed in cancer cell lines overexpressing ERBB2. In this report, we examined the cooperative effect of Yin Yang 1 (YY1) on AP-2-induced activation of ERBB2 promoter activity. We detected high levels of YY1 transcription factor in mammary cancer cell lines. Notably, we showed that YY1 enhances AP-2alpha transcriptional activation of the ERBB2 promoter through an AP-2 site both in HepG2 and in HCT116 cells, whereas a carboxyl-terminal-truncated form of YY1 cannot. Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line. In addition, inhibition of endogenous YY1 protein by an antisense decreased the transcription of an AP-2-responsive ERBB2 reporter plasmid in BT-474 breast cancer cells. Finally, we detected in vivo AP-2 and YY1 occupancy of the ERBB2 proximal promoter in chromatin immunoprecipitation assays. Our data thus provide evidence that YY1 cooperates with AP-2 to stimulate ERBB2 promoter activity through the AP-2 binding sites.
Giga-Cancer
Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (Communauté française de Belgique) - FRIA ; Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Fonds Léon Fredericq (Liège, Belgique) ; Télévie (Belgique) ; Centre Anticancéreux attaché à l'Université de Liège ; Fédération Belge contre le Cancer