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Sökning: WFRF:(All Ericsson Charlotta) > c-Kit-dependent gro...

  • All-Ericsson, CharlottaKarolinska Institutet (författare)

c-Kit-dependent growth of uveal melanoma cells : a potential therapeutic target?

  • Artikel/kapitelEngelska2004

Förlag, utgivningsår, omfång ...

  • Association for Research in Vision and Ophthalmology (ARVO),2004
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-10325
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-10325URI
  • https://doi.org/10.1167/iovs.03-1196DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:1955712URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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

  • Adult
  • Aged
  • Aged; 80 and over
  • Blotting; Western
  • Cell Division
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Melanoma/*metabolism/*pathology
  • Middle Aged
  • Paraffin Embedding
  • Phosphorylation/drug effects
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-kit/genetics/*metabolism
  • Pyrimidines/pharmacology
  • RNA; Messenger/metabolism
  • Skin Neoplasms/metabolism/pathology
  • Tumor Cells; Cultured
  • Tyrosine/metabolism
  • Uveal Neoplasms/*metabolism/*pathology
  • MEDICINE
  • MEDICIN

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Girnita, LeonardKarolinska Institutet (författare)
  • Müller-Brunotte, Anja (författare)
  • Brodin, BerthaKarolinska Institutet (författare)
  • Seregard, StefanKarolinska Institutet (författare)
  • Östman, ArneKarolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning (författare)
  • Larsson, OlleKarolinska Institutet (författare)
  • Karolinska InstitutetLudwiginstitutet för cancerforskning (creator_code:org_t)

Sammanhörande titlar

  • 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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