Abstract
The LKB1 tumor suppressor gene, mutated in Peutz-Jeghers syndrome, encodes a serine/threonine kinase of unknown function. Here we show that mice with a targeted disruption of Lkb1 die at midgestation, with the embryos showing neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development was also severely affected; the mutant placentas exhibited defective labyrinth layer development and the fetal vessels failed to invade the placenta. These phenotypes were associated with tissue-specific deregulation of vascular endothelial growth factor (VEGF) expression, including a marked increase in the amount of VEGF messenger RNA. Moreover, VEGF production in cultured Lkb1-/- fibroblasts was elevated in both normoxic and hypoxic conditions. These findings place Lkb 1 in the VEGF signaling pathway and suggest that the vascular defects accompanying Lkb 1 loss are mediated at least in part by VEGF.
Original language | English (US) |
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Pages (from-to) | 1323-1326 |
Number of pages | 4 |
Journal | Science |
Volume | 293 |
Issue number | 5533 |
DOIs | |
State | Published - Aug 17 2001 |
ASJC Scopus subject areas
- General