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Cancer Lett. 2009 May 18;277(2):149-54. doi: 10.1016/j.canlet.2008.11.036. Epub 2009 Jan 14.

Chemopreventive efficacy of rapamycin on Peutz-Jeghers syndrome in a mouse model.

Author information

1
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 1155 Pressler Boulevard, Houston, TX 77030, USA.

Abstract

Germline mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder with a predisposition to gastrointestinal polyposis and cancer. Hyperactivation of mTOR-signaling has been associated with PJS. We previously reported that rapamycin treatment of Lkb1(+/-) mice after the onset of polyposis reduced the polyp burden. Here we evaluated the preventive efficacy of rapamycin on Peutz-Jeghers polyposis. We found that rapamycin treatment of Lkb1(+/-) mice initiated before the onset of polyposis in Lkb1(+/-) mice led to a dramatic reduction in both polyp burden and polyp size and this reduction was associated with decreased phosphorylation levels of S6 and 4EBP1. Together, these findings support the use of rapamycin as an option for chemoprevention and treatment of PJS.

PMID:
19147279
PMCID:
PMC2966387
DOI:
10.1016/j.canlet.2008.11.036
[Indexed for MEDLINE]
Free PMC Article

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