Transcriptomics

Dataset Information

23

Differentiation of Mammary Tumors by SKI-606 (bostutinib) (gene expression)


ABSTRACT: While c-Src is infrequently mutated in human cancers, it mediates oncogenic signals of many activated growth factor receptors and thus remains a key potential target of cancer therapy. However, the widespread function of Src in many cell types and processes requires evaluation of Src-targeted therapeutics within a normal developmental and immune competent environment. In an effort to direct clinical use of Src inhibitors, we tested the effectiveness of one of the four Src inhibitors in clinical testing, SKI-606 (bosutinib), in the MMTV-PyVmT transgenic mouse model of breast cancer. Tumor formation in this model is dependent on the presence of Src, but the necessity of Src kinase activity for tumor formation has not been determined. Furthermore, Src inhibitors have not been examined in an autochthonous tumor model. Here we show that oral administration of the Src inhibitor SKI-606 inhibited the phosphorylation of Src in mammary tumors, and caused a rapid decrease in the Ezh2 Polycomb group histone H3K27 methyltransferase and an increase in epithelial organization. SKI-606 prevented the appearance of palpable tumors in more than half of the animals treated from puberty and stopped tumor growth in older animals with preexisting tumors. These antitumor effects were accompanied by decreased cellular proliferation, altered tumor blood vessel organization and dramatically increased differentiation to lactational and epidermal cell fates. SKI-606 controls the development of mammary tumors in this model by inducing differentiation. Overall design: Differentiation of Mammary Tumors by SKI-606 (bostutinib)

INSTRUMENT(S): [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

ORGANISM(S): Mus musculus  

SUBMITTER: Roy M Williams  

PROVIDER: GSE22150 | GEO | 2011-01-01

SECONDARY ACCESSION(S): PRJNA127709

REPOSITORIES: GEO

Similar Datasets

2010-09-15 | E-GEOD-20921 | ArrayExpress
2011-01-01 | E-GEOD-22150 | ArrayExpress
2010-09-15 | GSE20921 | GEO
| PRJNA124471 | ENA
| PRJNA127709 | ENA
| GSE107553 | GEO
2015-03-06 | E-GEOD-50517 | ArrayExpress
2010-12-01 | GSE20718 | GEO
2010-12-01 | E-GEOD-20718 | ArrayExpress
2013-06-02 | E-GEOD-37954 | ArrayExpress