The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Vascular Abnormalities and Deregulation of VEGF in Lkb1 -Deficient Mice
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 Lkb1 in the VEGF signaling pathway and suggest that the vascular defects accompanying Lkb1 loss are mediated at least in part by VEGF.
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Cites
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981
Cited by
The LKB1-AMPK pathway: metabolism and growth control in tumour suppression
Shackelford, D. B., & Shaw, R. J. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2676 · Cited by 1,943
Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells
Nakada, D., Saunders, T. L., & Morrison, S. J. (2010) · Nature · doi:10.1038/nature09571 · Cited by 524
Zu, Y., Liu, L., Lee, M. Y. K., Xu, C., Liang, Y., Man, R. Y., Vanhoutte, P. M., & Wang, Y. (2010) · Circulation Research · doi:10.1161/circresaha.109.215483 · Cited by 303
Sakamoto, K., Göransson, O., Hardie, D. G., & Alessi, D. R. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00074.2004 · Cited by 299
Treyer, A., & Müsch, A. (2013) · Comprehensive Physiology · doi:10.1002/cphy.c120009 · Cited by 252
Metadata
- Authors
- Ylikorkala, A., Rossi, D. J., Korsisaari, N., Luukko, K., Alitalo, K., Henkemeyer, M., & Mäkelä, T. P.
- Venue
- Science
- Published
- 2001-08-17
- Volume
- 293
- Issue
- 5533
- Pages
- 1323-1326
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2032607892
- Cited by
- 297
- References
- 1
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
