title: A soluble 17 kDa tumour necrosis factor (TNF) mutein, TNF-SAM2, with membrane-bound TNF-like biological characteristics.
abstract: BACKGROUND
  Membrane-bound tumour necrosis factor (TNF) has a different binding affinity to two TNF receptors (TNFR1 and TNFR2) and shows different biological activities compared with TNF-alpha. We have developed a mutein, TNF-SAM2, which has modified TNF-alpha. It has higher tumour killing activity than TNF-alpha and fewer side effects.
  
  
  METHODS
  The difference between TNF-SAM2 and TNF-alpha was examined in view of the binding affinity to each TNF receptor, cytotoxicity and expression of genes using Colo205 cells.
  
  
  RESULTS
  The KD value of TNF-alpha (2. 9x1-7 M) for TNFR1 was lower than TNF-SAM2 (6.9x10(-7) M). Cytotoxicity of TNF-SAM2 was significantly higher than for TNF-a. RNA of Colo205 cells stimulated with TNF-SAM2 indicated that 80 genes increased by a factor of 2 or more, and 69 genes decreased.
  
  
  CONCLUSIONS
  TNF-SAM2 can induce different intracellular signal transduction in Colo205 cells compared with TNF-alpha. TNF-SAM2 may have characteristics of the membrane-bound form despite the fact that is in a soluble form.
authors.affiliation: Faculty of Engineering, The University of Tokushima, Tokushima-shi, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshida
authors.forename: Chie
authors.initials: C
authors.lastname: Kohchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inagawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishizawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hori
authors.forename: Gen-Ichiro
authors.initials: G
authors.lastname: Soma
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C109083:TNF-SAM2; D014409:Tumor Necrosis Factor-alpha