Interleukin-7 receptor expression and activation in nonhaematopoietic neoplastic cell lines

Larry Cosenza, Gullu Gorgun, Alexander Urbano, Francine Foss

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The high-affinity human interleukin-7 (IL-7)R is a heterodimeric complex consisting of the IL-7Rα and common interleukin-2 receptor γ (IL-2Rγc) 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-2Rγc and p59 fyn, suggesting that the components of an IL-7R signalling network are present in nonhaematopoietic neoplastic cells. Immunoprecipitation of IL-7Rα 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.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalCellular Signalling
Volume14
Issue number4
DOIs
StatePublished - Mar 4 2002

Keywords

  • Interleukin-7
  • Jak kinases
  • Receptor
  • Signal transduction
  • fyn

ASJC Scopus subject areas

  • Cell Biology

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