We identified a new gene, called p8, which showed a strong induction during the acute phase of pancreatitis. Further experiments have shown that p8 mRNA is activated in response to several stresses and that its activation is not restricted to pancreatic cells. p8 is a nuclear protein and biochemical and biophysical studies showed that p8 was in many structural aspects very similar to the HMG (high mobility group) proteins, although sharing with them low amino acid sequence homology. Also, p8 was found overexpressed in many human cancers. Therefore, we wondered whether the p8-mediated response to cellular stress was necessary for tumor establishment. Subcutaneous or intraperitoneal injections of transformed p8-expressing fibroblasts led to tumor formation in nude mice, but no tumor was observed with transformed p8-deficient cells. Restoring p8 expression in transformed p8-deficient fibroblasts led to tumor formation demonstrating that p8 expression is necessary for tumor development and suggesting that the stress-response mechanisms governed by p8 are required for tumor establishment.