Stepwise acquisition of Trp53 mutation following Fbxw7 loss in a model of breast cancer. Fbxw7 is a tumor suppressor that targets several key oncogenes, and also the tumor suppressor p53. Meyer et al. have identified that Fbxw7 loss leads to lactation and involution defects in mice, and eventually to mammary tumors. This is associated with increased cyclin E1 and c-Myc activity, along with DNA damage. A second hit of Trp53 mutation is probably induced by the increase in DNA damage, and will overcome any induction of p53 activity downstream of Fbxw7 loss.
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