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

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.

• Authors: Chongjuan Wei, Christopher I Amos, Nianxiang Zhang, Jing Zhu, Xiaopei Wang, Marsha L Frazier
• Journal: Cancer letters (Cancer Lett) Vol. 277 Issue 2 Pg. 149-54 (May 18 2009) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 19147279 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibiotics, Antineoplastic
• Carrier Proteins
• Phosphotransferases (Alcohol Group Acceptor)
• mTOR protein, mouse
• Protein Serine-Threonine Kinases
• Stk11 protein, mouse
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases
• Sirolimus

Topics

• AMP-Activated Protein Kinases
• Animals
• Antibiotics, Antineoplastic (therapeutic use)
• Carrier Proteins (physiology)
• Disease Models, Animal
• Germ-Line Mutation
• Intestinal Polyps (genetics, pathology, prevention & control)
• Mice
• Mice, Knockout
• Peutz-Jeghers Syndrome (genetics, pathology, prevention & control)
• Phosphorylation
• Phosphotransferases (Alcohol Group Acceptor) (physiology)
• Protein Serine-Threonine Kinases (genetics)
• Signal Transduction
• Sirolimus (therapeutic use)
• TOR Serine-Threonine Kinases