Expression and regulation of c-kit receptor and response to stem cell factor in childhood malignant T-lymphoblastic cells.
The cytokine stem cell factor (SCF) synergizes with IL-7 to enhance the proliferation of thymocytes. We therefore investigated the role of the SCF receptor, the protooncogene c-kit, in the pathogenesis of pediatric T-lineage malignancies. Expression and regulation of c-kit in cells from children with non-Hodgkin's lymphoma (T-NHL) or acute lymphoblastic leukemia (T-ALL) and the proliferative effect of SCF on these cells were examined in seven cell lines and 21 biopsy tumor cell preparations. Inducibility of c-kit receptors by SCF, IL-1beta, IL-2, IL-7, TGF-beta, TNF-alpha, PMA or calcium ionophore A23187 was studied by flow cytometry (FCM). C-kit receptors were detected in three out of seven T-lymphoblastic cell lines and in nine out of 21 biopsy tumor cell preparations. Upregulation of c-kit could be induced by cultivation, and to a higher extent by cultivation and addition of IL-1beta, TNF-alpha, TGF-beta or A23187. Downregulation of c-kit occurred in the presence of SCF or PMA. SCF caused a downregulation of c-kit receptors in eight of nine, and a proliferative response in three of 11 c-kit-positive T-lymphoblastic cell preparations. We conclude that c-kit is able to transduce a growth stimulatory signal in some T-lymphoblastic cells and that its expression may not be detectable in a resting metabolic or proliferative state.
Department of Pediatric Hematology and Oncology, Medical School Hannover, Germany.
J
J
Tomeczkowski
D
D
Frick
B
B
Schwinzer
N
N
Wittner
W D
WD
Ludwig
A
A
Reiter
K
K
Welte
K W
KW
Sykora
D018952:Antigens, CD34 / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002648:Child; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D008970:Molecular Weight; D015260:Neprilysin / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018952:Antigens, CD34; D017252:CD3 Complex; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D015260:Neprilysin