Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests an autocrine/paracrine mechanism
| Autor: | Lars Rönnstrand, Séverine Tabone, Jean-François Emile, N Theou-Anton, D Brouty-Boye, Raphaël Saffroy, Antoinette Lemoine |
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| Rok vydání: | 2006 |
| Předmět: |
Gene isoform
Cancer Research sarcoma Gastrointestinal Stromal Tumors Blotting Western Enzyme-Linked Immunosorbent Assay Stem cell factor Sensitivity and Specificity Receptor tyrosine kinase autocrine loop Paracrine Communication Tumor Cells Cultured Humans RNA Messenger Molecular Diagnostics neoplasms gastrointestinal tumour Stem Cell Factor Oncogene biology GiST Reverse Transcriptase Polymerase Chain Reaction SCF Immunohistochemistry digestive system diseases Blot Autocrine Communication Proto-Oncogene Proteins c-kit Oncology Mutation biology.protein Cancer research |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6603063 |
| Popis: | KIT is a tyrosine kinase receptor expressed by several tumours, which has for specific ligand the stem cell factor (SCF). KIT is the main oncogene in gastrointestinal stromal tumours (GISTs), and gain-of-function KIT mutations are present in 70% of these tumours. The aim of the study was to measure and investigate the mechanisms of KIT activation in 80 KIT-positive GIST patients. KIT activation was quantified by detecting phosphotyrosine residues in Western blotting. SCF production was determined by reverse transcriptase-PCR, ELISA and/or immunohistochemistry. Primary cultures established from three GISTs were also analysed. The results show that KIT activation was detected in all cases, even in absence of KIT mutations. The fraction of activated KIT was not correlated with the mutational status of GISTs. Membrane and soluble isoforms of SCF mRNA were present in all GISTs analysed. Additionally, SCF was also detected in up to 93% of GISTs, and seen to be present within GIST cells. Likewise, the two SCF mRNA isoforms were found to be expressed in GIST-derived primary cultures. Thus, KIT activation in GISTs may in part result from the presence of SCF within the tumours. |
| Databáze: | OpenAIRE |
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