Although we saw a regulation of p21 by Notch3 both in tumors and in vitro in cells over-expressing Notch3, no evidence in the literature point to a role of senescence in the initiation step of tumorigenesis in the MMTV-Neu mice model but this would require further investigations as the increased proliferation of cancer cells observed in Notch3-null tumor may be associated with an early bypass of senescence. The gene discussed is NOTCH3; the disease is cancer.