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Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals

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Abstract

Microarray studies revealed that as a first hit the SV40 T/t antigen causes deregulation of 462 genes in mammary gland cells (ME cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell proliferation specific and Rb-E2F dependent, causing ME cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal ME cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal ME cells. The profile of retransformants shows that only 38 deregulated genes are tumor-specific, and that none of them is considered to be a typical breast cancer gene.

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Abbreviations

CA :

Correspondence analysis

DMEM :

Dulcecco’s modified Eagle medium

IRF :

Interferon regulatory factor

ME :

Mammary gland epithelial

OAS :

2′-5′-Oligoadenylate synthetase family members

PBS :

Phosphate-buffered saline

SV40 :

Simian virus 40

WAP :

Whey acidic milk protein

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Acknowledgements

This work was supported by the Verband der Chemischen Industrie. We thank Dr. A. Corfield for critical reading of the manuscript.

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Authors and Affiliations

  1. Institut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin, Arnimallee 22, 14195, Berlin, Germany

    Andreas Klein, Eva Guhl, Ralf Wessel, Monika Graessmann & Adolf Graessmann

  2. Institut für Pathologie, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    Raphael Zollinger & Michael Hummel

  3. Graduate Institute of Molecular and Cell Biology, Tzu-Chi University, 970, Hualien, Taiwan

    Yin-Jeh Tzeng

Authors
  1. Andreas Klein
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  2. Eva Guhl
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  3. Raphael Zollinger
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  4. Yin-Jeh Tzeng
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  5. Ralf Wessel
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  8. Adolf Graessmann
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Correspondence to Adolf Graessmann.

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Klein, A., Guhl, E., Zollinger, R. et al. Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals. J Mol Med 83, 362–376 (2005). https://doi.org/10.1007/s00109-004-0625-1

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  • DOI: https://doi.org/10.1007/s00109-004-0625-1

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