title: Interleukin-7 up-regulates cyclin D1 via activator protein-1 to promote proliferation of cell in lung cancer.
abstract: Interleukin-7 is a potent regulator of lymphocyte proliferation, but it inducing growth of solid tumors is few known. We study the relationship between Interleukin-7 and the regulator of the cell cycle, cyclin D1 and the mechanism of Interleukin-7 regulating cell growth in human lung cancer. We detected expression of cyclin D1 and its impact on the prognosis of lung cancer patients. Using Western blot, reverse transcriptase-PCR, Co-Immunoprecipitation, and Chromatin Immunoprecipitation, we investigated how Interleukin-7 regulated cyclin D1 in vitro and in nude mice. We found that, in lung cancer cell lines and in nude mice, Interleukin-7/Interleukin-7 receptor increased the expression of cyclin D1 and phosphorylation of c-Fos/c-Jun, induce c-Fos and c-Jun heterodimer formation, and enhanced c-Fos/c-Jun DNA-binding activity to regulate cyclin D1. In addition, lymph node metastasis, tumor stage, and cyclin D1 were the strongest predictors of survival in 100 human non-small cell lung cancer specimens analyzed. Taken together, our results provided evidence that Interleukin-7/Interleukin-7 receptor induced cyclin D1 up-regulation via c-Fos/c-Jun pathway to promote proliferation of cells in lung cancer.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, No. 92 North Second Road, Heping District, Shenyang 110001, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ming
authors.forename: Guocheng
authors.initials: G
authors.lastname: Jiang
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xueshan
authors.initials: X
authors.lastname: Qiu
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D015851:Interleukin-7; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D020395:Receptors, Interleukin-7; D018808:Transcription Factor AP-1; D019938:Cyclin D1; D048031:JNK Mitogen-Activated Protein Kinases