Growth suppression by Lkb1 is mediated by a G(1) cell cycle arrest

Germ-line mutations of LKB1 (STK11) lead to Peutz-Jeghers syndrome characte rized by gastrointestinal polyps and cancer of different organ systems. The mutations lead to loss or severe impairment of Lkb1 serine/threonine kinas e activity. Therefore LKB1 has been implicated as a tumor suppressor gene, but only a few mutations in the coding exons of LKB1 have been detected in sporadic tumors. Here, we have identified tumor cell lines with severely re duced mRNA levels and impaired Lkb1 kinase activity. Reintroducing Lkb1 int o these cells suppressed cell growth. The Lkb1-mediated growth inhibition w as caused by a G(1) cell cycle block and was not detected with several natu rally occurring Lkb1 mutants. These results indicate that LKB1 has function al and specific growth-suppressing activity.