Linked Life Data

15145934

Source:http://linkedlifedata.com/resource/pubmed/id/15145934

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2004-7-19
pubmed:abstractText
The B-Raf(V599E)-mediated constitutive activation of ERK1/2 is involved in establishing the transformed phenotype of some uveal melanoma cells (Calipel, A., Lefevre, G., Pouponnot, C., Mouriaux, F., Eychene, A., and Mascarelli, F. (2003) J. Biol. Chem. 278, 42409-42418). We have shown that stem cell factor (SCF) is involved in the proliferation of normal uveal melanocytes and that c-Kit is expressed in 75% of primary uveal melanomas. This suggests that the acquisition of autonomous growth during melanoma progression may involve the SCF/c-Kit axis. We used six human uveal melanoma tumor-derived cell lines and normal uveal melanocytes to characterize the SCF/c-Kit system and to assess its specific role in transformation. We investigated the possible roles of activating mutations in c-KIT, the overexpression of this gene, and ligand-dependent c-Kit overactivation in uveal melanoma cell tumorigenesis. Four cell lines (92.1, SP6.5, Mel270, and TP31) expressed both SCF and c-Kit, and none harbored the c-KIT mutations in exons 9, 11, 13, and 17 that have been shown to induce SCF-independent c-Kit activation. Melanoma cell proliferation was strongly inhibited by small interfering RNA-mediated depletion of c-Kit in these cells, despite the presence of (V599E)B-Raf in SP6.5 and TP31 cells. We characterized the signaling pathways involved in SCF/c-Kit-mediated cell growth and survival in normal and tumoral melanocytes and found that constitutive ERK1/2 activation played a key role in both the SCF/c-Kit autocrine loop and the gain of function of (V599E)B-Raf for melanoma cell proliferation and transformation. We also provide the first evidence that Glivec/STI571, a c-Kit tyrosine kinase inhibitor, could be used to treat uveal melanomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31769-79
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15145934-Base Sequence, pubmed-meshheading:15145934-Cell Division, pubmed-meshheading:15145934-Cell Line, Tumor, pubmed-meshheading:15145934-Cell Transformation, Neoplastic, pubmed-meshheading:15145934-DNA Primers, pubmed-meshheading:15145934-Gene Expression, pubmed-meshheading:15145934-Humans, pubmed-meshheading:15145934-Melanocytes, pubmed-meshheading:15145934-Melanoma, pubmed-meshheading:15145934-Mitogens, pubmed-meshheading:15145934-Mutation, pubmed-meshheading:15145934-Piperazines, pubmed-meshheading:15145934-Proto-Oncogene Proteins c-kit, pubmed-meshheading:15145934-Pyrimidines, pubmed-meshheading:15145934-RNA, Small Interfering, pubmed-meshheading:15145934-Signal Transduction, pubmed-meshheading:15145934-Stem Cell Factor, pubmed-meshheading:15145934-Uvea, pubmed-meshheading:15145934-Uveal Neoplasms
pubmed:year
2004
pubmed:articleTitle
Roles of stem cell factor/c-Kit and effects of Glivec/STI571 in human uveal melanoma cell tumorigenesis.
pubmed:affiliation
INSERM U598, Institut Biomédical des Cordeliers, 75006 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't