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c-Kit-dependent gro...
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All-Ericsson, CharlottaKarolinska Institutet
(författare)
c-Kit-dependent growth of uveal melanoma cells : a potential therapeutic target?
- Artikel/kapitelEngelska2004
Förlag, utgivningsår, omfång ...
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Association for Research in Vision and Ophthalmology (ARVO),2004
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-10325
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-10325URI
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https://doi.org/10.1167/iovs.03-1196DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:1955712URI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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PURPOSE: This study was conducted to investigate the expression and functional impact of the proto-oncogene c-kit in uveal melanoma. METHODS: Based on immunohistochemical (IHC) study of paraffin-embedded specimens from 134 uveal melanomas and Western blot analysis on eight fresh-frozen samples the expression of c-kit in uveal melanoma was studied. Furthermore, the phosphorylation of c-kit and the impact of the tyrosine kinase inhibitor STI571 was examined in the three uveal melanoma cell lines OCM-1, OCM-3, and 92-1. RESULTS: Eighty-four of 134 paraffin-embedded samples and six of eight fresh-frozen samples expressed c-kit. c-Kit was strongly expressed and tyrosine phosphorylated in cultured uveal melanoma cells compared with cutaneous melanoma cells. Moreover, in contrast to cutaneous melanoma cell lines c-kit maintained a high phosphorylation level in serum-depleted uveal melanoma cells. No activation-related mutations in exon 11 of the KIT gene were found. On the contrary, expression of the stem cell growth factor (c-kit ligand) was detected in all three uveal melanoma cell lines, suggesting the presence of autocrine (paracrine) stimulation pathways. Treatment of uveal melanoma cell lines with STI571, which blocks c-kit autophosphorylation, resulted in cell death. The IC(50) of the inhibitory effects on c-kit phosphorylation and cell proliferation was of equal size and less than 2.5 microM. CONCLUSIONS: The results confirm that c-kit is vastly expressed in uveal melanoma, suggest that the c-kit molecular pathway may be important in uveal melanoma growth, and point to its use as a target for therapy with STI571.
Ämnesord och genrebeteckningar
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Adult
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Aged
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Aged; 80 and over
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Blotting; Western
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Cell Division
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Female
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Humans
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Immunoenzyme Techniques
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Male
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Melanoma/*metabolism/*pathology
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Middle Aged
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Paraffin Embedding
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Phosphorylation/drug effects
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Polymerase Chain Reaction
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Proto-Oncogene Proteins c-kit/genetics/*metabolism
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Pyrimidines/pharmacology
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RNA; Messenger/metabolism
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Skin Neoplasms/metabolism/pathology
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Tumor Cells; Cultured
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Tyrosine/metabolism
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Uveal Neoplasms/*metabolism/*pathology
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Girnita, LeonardKarolinska Institutet
(författare)
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Müller-Brunotte, Anja
(författare)
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Brodin, BerthaKarolinska Institutet
(författare)
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Seregard, StefanKarolinska Institutet
(författare)
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Östman, ArneKarolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning
(författare)
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Larsson, OlleKarolinska Institutet
(författare)
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Karolinska InstitutetLudwiginstitutet för cancerforskning
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Investigative Ophthalmology and Visual Science: Association for Research in Vision and Ophthalmology (ARVO)45:7, s. 2075-820146-04041552-5783
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