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c-Kit-dependent gro...
c-Kit-dependent growth of uveal melanoma cells : a potential therapeutic target?
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- All-Ericsson, Charlotta (författare)
- Karolinska Institutet
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- Girnita, Leonard (författare)
- Karolinska Institutet
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Müller-Brunotte, Anja (författare)
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- Brodin, Bertha (författare)
- Karolinska Institutet
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- Seregard, Stefan (författare)
- Karolinska Institutet
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- Östman, Arne (författare)
- Karolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Larsson, Olle (författare)
- Karolinska Institutet
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(creator_code:org_t)
- Association for Research in Vision and Ophthalmology (ARVO), 2004
- 2004
- Engelska.
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 45:7, s. 2075-82
- Relaterad länk:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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