Peutz-Jeghers syndrome is an inherited disorder characterized by the development of gastrointestinal polyps and increased risk of cancer. The causative mutations lie in the Lkb1 gene, which encodes a serine-threonine kinase. To gain insight into the function of LKB1, Ylikorkala et al. created mice deficient in the kinase. The absence of LKB1 was lethal to embryos and was associated with severe defects in the development of the vasculature and aberrant, increased expression of vascular endothelial growth factor (VEGF). These results suggest that LKB1's role as a tumor suppressor may in part be due to its ability to prevent growth of the blood vessels that are needed for tumor progression.
A. Ylikorkala, D. J. Rossi, N. Korsisaari, K. Luukko, K. Alitalo, M. Henkemeyer, T. P. Mäkelä, Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Science 293, 1323-1326 (2001). [Abstract] [Full Text]