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

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

All-Ericsson, Charlotta (författare)
Karolinska Institutet
Girnita, Leonard (författare)
Karolinska Institutet
Müller-Brunotte, Anja (författare)
visa fler...
Brodin, Bertha (författare)
Karolinska Institutet
Seregard, Stefan (författare)
Karolinska Institutet
Östman, Arne (författare)
Karolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning
Larsson, Olle (författare)
Karolinska Institutet
visa färre...
 (creator_code:org_t)
Association for Research in Vision and Ophthalmology (ARVO), 2004
2004
Engelska.
Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 45:7, s. 2075-82
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

Nyckelord

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

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