title: [Interleukin 7 and its receptor promote cell proliferation and induce lymphangiogenesis in non-small cell lung cancer].
abstract: OBJECTIVE
  To study the mechanism of interleukin 7/interleukin 7 receptor (IL-7/IL-7R) in promoting cell proliferation and inducing lymphangiogenesis of non-small cell lung cancer (NSCLC) in vivo and in vitro.
  
  
  METHODS
  Immunohistochemical study for IL-7, IL-7R, cyclin D1 and vascular endothelial growth factor-D (VEGF-D) was carried out in NSCLC tissues from 95 patients. The relationship between IL-7/IL-7R expression and various parameters was analyzed. The mechanism of IL-7/IL-7R in promoting cell proliferation and inducing lymphangiogenesis was studied by methylthiazolyldiphenyl-tetrazolium bromide, fluorescence-activated cell sorting, reverse transcriptase-PCR, Western blot, co-immunoprecipitation, chromatin immunoprecipitation and nude mice experiments with xenograft tumors.
  
  
  RESULTS
  IL-7 (63.2%, 60/95), IL-7R (61.1%, 58/95), cyclin D1 (52.6%, 50/95) and VEGF-D (58.9%, 56/95) showed that high level of expression in NSCLC. IL-7/IL-7R over-expression correlated with cyclin D1 expression (P < 0.01, P < 0.01), VEGF-D expression (P < 0.01, P < 0.01), increased lymphovascular density (P = 0.005, P = 0.013), advanced clinical stage (P = 0.008, P = 0.005) and presence of lymph node metastasis (P < 0.01, P < 0.01). IL-7/IL-7R could promote proliferation of A549 cell, increase cyclin D1 and VEGF-D expression, and enhance c-Fos/c-Jun expression and phosphorylation, resulting in formation of heterodimer. Furthermore, IL-7/IL-7R could induce binding of c-Fos/c-Jun to cyclin D1/VEGF-D promoters and regulate their transcription. IL-7/IL-7R could also promote proliferation and lymphangiogenesis of lung cancer xenograft tumors.
  
  
  CONCLUSIONS
  IL-7/IL-7R promotes c-Fos/c-Jun expression and activity in NSCLC. This further facilitates cyclin D1 expression and accelerates proliferation of cells and VEGF-D-induced lymphovascular formation.
authors.affiliation: Department of Pathology, College of Basic Medical Science, China Medical University, Shenyang 110001, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ming
authors.forename: Qing-fu
authors.initials: QF
authors.lastname: Zhang
authors.forename: Yan-duo
authors.initials: YD
authors.lastname: Jiang
authors.forename: Guo-cheng
authors.initials: GC
authors.lastname: Jiang
authors.forename: Xue-shan
authors.initials: XS
authors.lastname: Qiu
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism* / Q000502:physiology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism* / Q000502:physiology; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C508605:IL7 protein, human; D015851:Interleukin-7; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D020395:Receptors, Interleukin-7; D042643:Vascular Endothelial Growth Factor D; D019938:Cyclin D1