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Learn MoreModel: The activation of Ret receptor tyrosine kinase regulates mammary tumor growth, tumor-associated inflammation and metastasis. To uncover Rets function, we have generated a new transgenic mouse mammary tumor model, in which the human wild type Ret is expressed in the mammary epithelium of mice in a doxycycline (Dox)-inducible manner (system developed by Dr. Chosdosh). Induction of constitutive Ret expression leads to the development of mammary tumors in 60% of the mice. We have found that the Ret-induced tumors have histologic characteristics of the human DCIS. Purpose: The goals of this study are to compare Next-generation sequencing (NGS)-derived transcriptome profiling (RNA-seq) of Ret-induced tumors to human breast cancer databases in order to determined which cancer subtype is represented by this new tumor model. Additionally, to further analyze the mechanisms underlying Ret-induced tumorigenesis, we will also examine the transcriptome by NGS: in this case, this analysis will be performed on tumors that regress upon dox-food withdrawal, in comparison to the growing tumors. We will also perform similar analysis with the hyperplastic glands, a step before of tumor development. Later, the RNA-seq differential expression data will be analyzed using pathway analysis software as Ingenuity and public available datasets as the Gene Set Enrichment Analysis (GSEA) or the Integrating Motif Response Activity Analysis (ISMARA). SOURCE: Tim Roloff (tim.roloff@fmi.ch) - FMI
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