TUMOR-NECROSIS-FACTOR ACTS AS A TUMOR PROMOTER IN BALB 3T3 CELL-TRANSFORMATION/

Tumor necrosis factor (TNF), a cytokine, and okadaic acid, a tumor pro moter, strongly phosphorylated the same proteins, vimentin and heat sh ock 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-a lpha was about 1000 times more effective than the chemical tumor promo ters, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate. TNF induc ed growth of v-Ha-ras transfected BALB/3T3 cells (Bhas 42 cells), wher eas it did not induce growth of nontransfected BALB/3T3 cells. Okadaic acid induced mouse TNF-alpha from Bhas 42 and BALB/3T3 cells. The res ults suggest that a chemical tumor promoter induces the secretion of T NF-alpha from various cells. The TNF then acts as an endogenous tumor promoter in vivo.