Growth suppression by Lkb1 is mediated by a G(1) cell cycle arrest.
Germ-line mutations of LKB1 (STK11) lead to Peutz-Jeghers syndrome characterized by gastrointestinal polyps and cancer of different organ systems. The mutations lead to loss or severe impairment of Lkb1 serine/threonine kinase 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 reduced mRNA levels and impaired Lkb1 kinase activity. Reintroducing Lkb1 into these cells suppressed cell growth. The Lkb1-mediated growth inhibition was caused by a G(1) cell cycle block and was not detected with several naturally occurring Lkb1 mutants. These results indicate that LKB1 has functional and specific growth-suppressing activity.
Tiainen
M
M
Haartman Institute and Biocentrum Helsinki, P.O. Box 21, 00014 University of Helsinki, Helsinki, Finland.
Ylikorkala
A
A
Mäkelä
T P
TP
D016475:3T3 Cells; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D019175:DNA Methylation; D005091:Exons; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008545:Melanoma; D051379:Mice; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000235:genetics; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; C491654:Stk11 protein, mouse; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases