Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.

Details

Serval ID
serval:BIB_169C9D973A2D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Journal
International Journal of Cancer. Journal International du Cancer
Author(s)
Otto B., Gruner K., Heinlein C., Wegwitz F., Nollau P., Ylstra B., Pantel K., Schumacher U., Baumbusch L.O., Martin-Subero J.I., Siebert R., Wagener C., Streichert T., Deppert W., Tolstonog G.V.
ISSN
1097-0215 (Electronic)
ISSN-L
0020-7136
Publication state
Published
Issued date
2013
Volume
132
Number
6
Pages
1300-1310
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish PDF type: Article
Abstract
Mammary carcinomas developing in SV40 transgenic WAP-T mice arise in two distinct histological phenotypes: as differentiated low-grade and undifferentiated high-grade tumors. We integrated different types of information such as histological grading, analysis of aCGH-based gene copy number and gene expression profiling to provide a comprehensive molecular description of mammary tumors in WAP-T mice. Applying a novel procedure for the correlation of gene copy number with gene expression on a global scale, we observed in tumor samples a global coherence between genotype and transcription. This coherence can be interpreted as a matched transcriptional regulation inherited from the cells of tumor origin and determined by the activity of cancer driver genes. Despite common recurrent genomic aberrations, e.g. gain of chr. 15 in most WAP-T tumors, loss of chr. 19 frequently occurs only in low-grade tumors. These tumors show features of "basal-like" epithelial differentiation, particularly expression of keratin 14. The high-grade tumors are clearly separated from the low-grade tumors by strong expression of the Met gene and by coexpression of epithelial (e.g. keratin 18) and mesenchymal (e.g. vimentin) markers. In high-grade tumors, the expression of the nonmutated Met protein is associated with Met-locus amplification and Met activity. The role of Met as a cancer driver gene is supported by the contribution of active Met signaling to motility and growth of mammary tumor-derived cells. Finally, we discuss the independent origin of low- and high-grade tumors from distinct cells of tumor origin, possibly luminal progenitors, distinguished by Met gene expression and Met signaling.
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2013 18:46
Last modification date
20/08/2019 13:46
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