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AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

Oncogene volume 19, pages 280–288 (2000)Cite this article

Abstract

Transcription of the ERBB2 oncogene is repressed by oestrogen in human breast cancer cells. We show that a 218 bp fragment of the human ERBB2 gene promoter is responsive to oestrogen in transient transfection in ZR75.1 and SKBR.3 cells when the oestrogen receptor is expressed. Deletion analysis of this fragment shows that a sequence located at the 5′ end, which is known to mediate ERBB2 overexpression in breast cancer, is also responsible for the oestrogen response. This sequence binds AP-2 transcription factors and appears functionally identical to an element of the oestrogen-dependent enhancer described in the first intron of human ERBB2. We observed that oestrogen treatment down-regulates expression of AP-2 proteins but does not affect the DNA binding activity of AP-2. Constitutive expression of AP-2β or AP-2γ, but not AP-2α, abrogates the estrogenic repression. Our results demonstrate that AP-2 transcription factors are implicated in the oestrogenic regulation of ERBB2 gene expression and suggest a complex interplay involving the different AP-2 isoforms and other unidentified factors.

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Acknowledgements

We thank Prof P Sismondi for providing logistic help and continuous support and encouragement and Ms E Wright for English revision. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro and by the Italian MURST.

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Author notes

  1. Valentina Perissi

    Present address: Howard Hughes Medical Institute, La Jolla, CA, USA

Authors and Affiliations

  1. Institute for Cancer Research and Treatment (IRCC), Str. Prov. 142, Km. 3.95, Candiolo, 10060, Italy

    Valentina Perissi, Erika Cottone & Michele De Bortoli

  2. Department of Animal and Human Biology, University of Turin, Italy

    Valentina Perissi, Nadia Menini, Erika Cottone, Daniela Capello, Marco Sacco, Fabrizio Montaldo & Michele De Bortoli

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  1. Valentina Perissi
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Perissi, V., Menini, N., Cottone, E. et al. AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen. Oncogene 19, 280–288 (2000). https://doi.org/10.1038/sj.onc.1203303

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