Linked Life Data

17952454

Source:http://linkedlifedata.com/resource/pubmed/id/17952454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-1-24
pubmed:abstractText
The expression of the H-ras oncogene increases the migratory activity of many cell types and thereby contributes to the metastatic behavior of tumor cells. Other studies point to an involvement of volume-activated anion channels (VRAC) in (tumor) cell migration. In this paper, we tested whether VRACs are required for the stimulation of cell migration upon expression of the H-ras oncogene. We compared VRAC activation and migration of wild-type and H-ras-transformed NIH3T3 fibroblasts by means of patch-clamp techniques and time-lapse video microscopy. Both cell types achieve the same degree of VRAC activation upon maximal stimulation, induced by reducing extracellular osmolarity from 300 to 190 mOsm/l. However, upon physiologically relevant reductions in extracellular osmolarity (275 mOsm/l), the level of VRAC activation is almost three times higher in H-ras-transformed compared to wild-type fibroblasts. This increase in VRAC sensitivity is accompanied by increased migratory activity of H-ras fibroblasts. Moreover, the high-affinity VRAC blocker NS3728 inhibits migration of H-ras fibroblasts dose-dependently by up to about 60%, whereas migration of wild-type fibroblasts is reduced by only about 35%. Consistent with higher VRAC activity in H-ras than in wild-type fibroblasts, more VRAC blocker is needed to achieve a comparable degree of inhibition of migration. We suggest that H-ras modulates the volume set point of VRAC and thus facilitates transient changes of cell volume required for faster cell migration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0031-6768
pubmed:author
pubmed:issnType
Print
pubmed:volume
455
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1055-62
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
H-ras transformation sensitizes volume-activated anion channels and increases migratory activity of NIH3T3 fibroblasts.
pubmed:affiliation
Department of Molecular Biology, University of Copenhagen, 13 Universitetsparken, 2100 Copenhagen, OE, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't