Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation.
Tumor necrosis factor (TNF), a cytokine, and okadaic acid, a tumor promoter, strongly phosphorylated the same proteins, vimentin and heat shock protein 27, although their time courses were different. Human TNF-alpha at a concentration of 0.6 nM markedly stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene. The human TNF-alpha was about 1000 times more effective than the chemical tumor promoters, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate. TNF induced growth of v-Ha-ras transfected BALB/3T3 cells (Bhas 42 cells), whereas it did not induce growth of nontransfected BALB/3T3 cells. Okadiac acid induced mouse TNF-alpha from Bhas 42 and BALB/3T3 cells. The results suggest that a chemical tumor promoter induces the secretion of TNF-alpha from various cells. The TNF then acts as an endogenous tumor promoter in vivo.
Komori
A
A
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Yatsunami
J
J
Suganuma
M
M
Okabe
S
S
Abe
S
S
Sakai
A
A
Sasaki
K
K
Fujiki
H
H
D016475:3T3 Cells / Q000473:pathology*; D000818:Animals; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004988:Ethers, Cyclic / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019319:Okadaic Acid; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D014746:Vimentin / Q000378:metabolism
D002273:Carcinogens; D004988:Ethers, Cyclic; D006360:Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; D014746:Vimentin; D019319:Okadaic Acid