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-α at a concentration of 0.6 nm markedly stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene. The human TNF-α 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. Okadaic acid induced mouse TNF-α from Bhas 42 and BALB/3T3 cells. The results suggest that a chemical tumor promoter induces the secretion of TNF-α from various cells. The TNF then acts as an endogenous tumor promoter in vivo .