People with the Peutz–Jeghers syndrome (PJS) have numerous intestinal polyps arising from a germline mutation in the Lkb1 gene. Intriguingly these polyps seldom become malignant, but the reason behind this resistance has remained unclear. In September 12 Nature, Nabeel Bardeesy and colleagues at Harvard Medical School, USA, show that the LKB1 is a context-dependent tumor suppressor gene, whose loss of function facilitates intestinal polyposis, but renders cells resistant to malignant transformation by powerful oncogenic combinations (Nature 2002, 419:162-167).

Bardeesy et al. generated mice that lacked one copy of Lkb1 and carried a second 'conditional' copy of the gene, which could be inactivated under specific experimental conditions. They observed that Lkb+/- mice develop intestinal polyps and Lkb1 deficiency prevented culture-induced senescence without loss of Ink4a/Arf or p53. In addition, they showed that Lkb-/- mice could not survive, but their embryonic fibroblasts showed resistance to malignant...

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