github link
Accession IconGSE50517

Shp2 Signaling Suppresses Senescence in PyMT-induced Mammary Gland Cancer in Mice [Mouse430_2 array]

Organism Icon Mus musculus
Sample Icon 15 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Submitter Supplied Information

Description
In this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of MMTV-PyMT mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence-associated -gal (SA--gal), cyclin-dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to inhibition of self-renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, Focal adhesion kinase and Map kinase inhibit senescence by activating the expression of S-phase kinase-associated protein 2 (Skp2), Aurora kinase A (Aurka), and the Notch ligand Delta-like 1 (Dll1), which block p27 and p53. Remarkably, the expression of Shp2 and of selected target genes predicts human breast cancer outcome. We conclude that therapies which rely on senescence induction by inhibiting Shp2 or controlling its target gene products may be useful in blocking breast cancer.
PubMed ID
Total Samples
15

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Specimen part
Treatment
Processing Information
Additional Metadata
No rows found
Loading...