title: Mechanisms by which interleukin-6 attenuates cell invasion and tumorigenesis in human bladder carcinoma cells.
abstract: Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cells in vitro and in vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasion in vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN), N-myc downstream gene 1 (NDRG1), and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan 33305, Taiwan.
authors.forename: Ke-Hung
authors.initials: KH
authors.lastname: Tsui
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Chung
authors.forename: Tsui-Hsia
authors.initials: TH
authors.lastname: Feng
authors.forename: Tzu-Yi
authors.initials: TY
authors.lastname: Lee
authors.forename: Phei-Lang
authors.initials: PL
authors.lastname: Chang
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051861:Kangai-1 Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014746:Vimentin / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D051861:Kangai-1 Protein; D015843:Serpins; D014746:Vimentin; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C497688:CD82 protein, human; C508600:IL6 protein, human; C085344:SERPIN-B5