Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals.
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.
Klein
Andreas
A
Institut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin, Arnimallee 22, 14195 Berlin, Germany.
Guhl
Eva
E
Zollinger
Raphael
R
Tzeng
Yin-Jeh
YJ
Wessel
Ralf
R
Hummel
Michael
M
Graessmann
Monika
M
Graessmann
Adolf
A
D000782:Aneuploidy; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming