Growth Suppression by Lkb1 Is Mediated by a G1 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,...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 96; no. 16; pp. 9248 - 9251
Main Authors Tiainen, Marianne, Ylikorkala, Antti, Mäkelä, Tomi P.
Format Journal Article
LanguageEnglish
Published Washington National Academy of Sciences of the United States of America 03.08.1999
National Acad Sciences
National Academy of Sciences
The National Academy of Sciences
Subjects
3T3 cells
Biological Sciences
Cancer
Cell cycle
Cell growth
Cell lines
Cells
Genes
Genetics
HEK293 cells
HeLa cells
Messenger RNA
Mutation
NIH 3T3 cells
Transfection
Tumors
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Summary: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. Reintroducting Lkb1 into these cells suppressed cell growth. The Lkb1-mediated growth inhibition was caused by a G1 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.
Bibliography:Edited by Webster K. Cavenee, University of California at San Diego, La Jolla, CA, and approved June 3, 1999
To whom reprint requests should be addressed. E-mail: tomi.makela@helsinki.fi.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.16.9248