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The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism.

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Boidot, R [] Végran, F [] Jacob, D [] Chevrier, S [] Cadouot, M [] Feron, Olivier [UCL] Lizard-Nacol, S []

Expression of survivin, a member of the inhibitor of apoptosis protein family, is elevated in human cancers and considered as a new therapeutic target. Mechanism upregulating survivin expression in tumour cells is poorly understood. In this study, we show that breast cancer patients harbouring a polymorphism G235A in the survivin promoter present a higher level of survivin expression. This polymorphism creates a binding site for the transcription factor GATA-1 inducing a second GATA-1-binding site in survivin promoter. At the mRNA level, GATA-1 was present in breast carcinomas and adjacent normal tissues, whereas the protein was only detected in carcinomas by western blot and immunohistochemistry. Transfection of wild-type and different constitutively active GATA-1 mutants (serine 26, 178 or 310) showed that only phospho-serine 26 GATA-1 was able to increase survivin expression. This increase was higher in G235A than in G235G cell lines. Phospho-serine 26 GATA-1 bound directly survivin promoter, with a stronger interaction in G235A than in G235G polymorphism indicating that both GATA-1-binding sites are functional. These data identify GATA-1 as a key feature in tumour aggressiveness by enhancing survivin expression and delineate its targeting as a possible new therapeutic strategy in breast carcinomas.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Publication date 2010
Language Anglais
Journal information "Oncogene : including Oncogene Reviews" - Vol. 29, no. 17, p. 2577-84 (2010)
Peer reviewed yes
Publisher Nature Publishing Group ((United Kingdom) London)
issn 0950-9232
e-issn 1476-5594
Publication status Publié
Affiliations UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
UCL - SSS/IREC - Institut de recherche expérimentale et clinique
MESH Subject Binding Sites ; Breast Neoplasms - chemistry, genetics ; Up-Regulation ; Cell Line, Tumor ; Female ; GATA1 Transcription Factor - physiology ; Humans ; Microtubule-Associated Proteins - genetics ; Phosphorylation ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic
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Bibliographic reference Boidot, R ; Végran, F ; Jacob, D ; Chevrier, S ; Cadouot, M ; et. al. The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism.. In: Oncogene : including Oncogene Reviews, Vol. 29, no. 17, p. 2577-84 (2010)
Permanent URL http://hdl.handle.net/2078.1/89948