Interleukin-7 receptor expression and activation in nonhaematopoietic neoplastic cell lines.
The high-affinity human interleukin-7 (IL-7)R is a heterodimeric complex consisting of the IL-7Ralpha and common interleukin-2 receptor gamma (IL-2Rgamma(c)) chains. Activation of the IL-7R complex is associated with tyrosine and serine residue phosphorylation of a number of intracellular substrates leading to proliferation and induction of various cellular differentiation processes. In this study, we demonstrate, by S1 nuclease protection assay, immunoprecipitation and in vitro kinase assay that functional human (h) IL-7R is expressed in haematopoietic and nonhaematopoietic cell lines. The National Cancer Institute (NCI) tumour panel of 60 cell lines (NCI60) was screened for the expression of IL-7R mRNA by S1 nuclease protection assay, and IL-7R mRNA was detected in 9 of 12 leukemia, 3 of 7 lung, 4 of 6 CNS, 2 of 7 melanoma, 2 of 7 renal, 1 of 6 colon and 1 of 6 breast cancer cell lines. Immunoblot analysis of haematopoietic, lung cancer and brain tumour cell lines demonstrated expression of IL-7R, IL-2Rgamma(c) and p59 fyn, suggesting that the components of an IL-7R signalling network are present in nonhaematopoietic neoplastic cells. Immunoprecipitation of IL-7Ralpha followed by an in vitro kinase assay demonstrated functional receptor phosphorylation events in the lung cancer cells but not in the brain tumour cell lines. The expression of functional IL-7R on epithelial tumour cells may represent a potential target for receptor-directed therapy.
Cosenza
Larry
L
Department of Medicine, Division of Hematology and Oncology, New England Medical Center, 750 Washington Street, Boston, MA 02111, USA.
Gorgun
Gullu
G
Urbano
Alexander
A
Foss
Francine
F
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D053631:Interleukin Receptor Common gamma Subunit; D053616:Janus Kinase 3; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D023282:Nuclease Protection Assays; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger / Q000096:biosynthesis; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D051076:Proto-Oncogene Proteins c-fyn