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Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma.

Gustafsson, Anna LU ; Boström, Anna-Karin LU ; Ljungberg, Börje; Axelson, Håkan LU and Dahlbäck, Björn LU (2009) In PLoS ONE 4(10).
Abstract
BACKGROUND: The molecular biology of renal cell carcinoma (RCC) is complex and not fully understood. We have recently found that the expression of the receptor tyrosine kinase Axl in the RCC tumors independently correlates with survival of the patients. PRINCIPAL FINDINGS: Here, we have investigated the role of Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, in clear cell RCC (ccRCC) derived cells. The Axl protein was highly expressed in ccRCC cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL reconstituted cells expressed decreased levels of Axl protein, but not Axl mRNA, suggesting VHL to regulate Axl expression.... (More)
BACKGROUND: The molecular biology of renal cell carcinoma (RCC) is complex and not fully understood. We have recently found that the expression of the receptor tyrosine kinase Axl in the RCC tumors independently correlates with survival of the patients. PRINCIPAL FINDINGS: Here, we have investigated the role of Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, in clear cell RCC (ccRCC) derived cells. The Axl protein was highly expressed in ccRCC cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL reconstituted cells expressed decreased levels of Axl protein, but not Axl mRNA, suggesting VHL to regulate Axl expression. Gas6-mediated activation of Axl in ccRCC cells resulted in Axl phosphorylation, receptor down-regulation, decreased cell-viability and migratory capacity. No effects of the Gas6/Axl system could be detected on invasion. Moreover, in ccRCC tumor tissues, Axl was phosphorylated and Gas6 gamma-carboxylated, suggesting these molecules to be active in vivo. SIGNIFICANCE: These results provide novel information regarding the complex function of the Gas6/Axl system in ccRCC. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
4
issue
10
publisher
Public Library of Science
external identifiers
  • wos:000271414300003
  • pmid:19888345
  • scopus:70449449665
ISSN
1932-6203
DOI
10.1371/journal.pone.0007575
language
English
LU publication?
yes
id
3059b174-dcb7-4f88-b997-4fd302c49210 (old id 1512262)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19888345?dopt=Abstract
date added to LUP
2009-12-01 11:36:12
date last changed
2017-12-10 04:20:53
@article{3059b174-dcb7-4f88-b997-4fd302c49210,
  abstract     = {BACKGROUND: The molecular biology of renal cell carcinoma (RCC) is complex and not fully understood. We have recently found that the expression of the receptor tyrosine kinase Axl in the RCC tumors independently correlates with survival of the patients. PRINCIPAL FINDINGS: Here, we have investigated the role of Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, in clear cell RCC (ccRCC) derived cells. The Axl protein was highly expressed in ccRCC cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL reconstituted cells expressed decreased levels of Axl protein, but not Axl mRNA, suggesting VHL to regulate Axl expression. Gas6-mediated activation of Axl in ccRCC cells resulted in Axl phosphorylation, receptor down-regulation, decreased cell-viability and migratory capacity. No effects of the Gas6/Axl system could be detected on invasion. Moreover, in ccRCC tumor tissues, Axl was phosphorylated and Gas6 gamma-carboxylated, suggesting these molecules to be active in vivo. SIGNIFICANCE: These results provide novel information regarding the complex function of the Gas6/Axl system in ccRCC.},
  articleno    = {e7575},
  author       = {Gustafsson, Anna and Boström, Anna-Karin and Ljungberg, Börje and Axelson, Håkan and Dahlbäck, Björn},
  issn         = {1932-6203},
  language     = {eng},
  number       = {10},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0007575},
  volume       = {4},
  year         = {2009},
}