Original Article

Journal of Molecular Medicine

, Volume 83, Issue 5, pp 362-376

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

  • Andreas KleinAffiliated withInstitut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin
  • , Eva GuhlAffiliated withInstitut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin
  • , Raphael ZollingerAffiliated withInstitut für Pathologie, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin
  • , Yin-Jeh TzengAffiliated withGraduate Institute of Molecular and Cell Biology, Tzu-Chi University
  • , Ralf WesselAffiliated withInstitut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin
  • , Michael HummelAffiliated withInstitut für Pathologie, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin
  • , Monika GraessmannAffiliated withInstitut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin
  • , Adolf GraessmannAffiliated withInstitut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin Email author 

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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.

Keywords

Breast cancer Mammary gland epithelial cells SV40 T/t antigen Tumorigenesis WAP-SVT/t transgene