Wip1-deficient mice are resistant to common cancer genes.
PPM1D encodes WIP1, a serine-threonine phosphatase that had previously been shown to be the driver oncogene of a 17q23 amplicon that is present in approximately 15% of human breast tumors. However, it is unknown whether it has any role in the remaining 85% of breast tumors. A recent study using Wip1-deficient mice revealed that blocking its function significantly impaired RAS and ERBB2-induced breast tumor formation, suggesting that the inhibition of Wip1 could be a broad-spectrum treatment for breast cancer. However, because of the structure of Wip1, the development of small molecule inhibitors is a significant challenge.
Tularik Ltd, Aleutian House, Tytherington Business Park, Macclesfield, Cheshire SK19 2XR, UK.
Martin
M
Harrison
Jing
J
Li
Yan
Y
Degenhardt
Timothy
T
Hoey
Scott
S
Powers
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000172:deficiency / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000502:physiology*; D000071636:Protein Phosphatase 2C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D009363:Neoplasm Proteins; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D018719:Erb-b2 Receptor Tyrosine Kinases; C000607458:PPM1D protein, human; C000607468:Ppm1d protein, mouse