Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests an autocrine/paracrine mechanism.
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.
INSERM U602, Villejuif, France.
N
N
Théou-Anton
S
S
Tabone
D
D
Brouty-Boyé
R
R
Saffroy
L
L
Ronnstrand
A
A
Lemoine
J-F
JF
Emile
D019898:Autocrine Communication; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D019899:Paracrine Communication; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019089:Stem Cell Factor / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit