TNF-alpha induction of A1 expression in human cancer cells.

A1, a member of the Bcl-2 gene family, was originally identified as a hemopoietic-specific early response gene. Later it was found that A1 was overexpressed in human stomach cancer tissues and was induced by tumor necrosis factor-alpha (TNF-alpha) in human vascular endothelial cells. However, its expression in human cancer cells has not been well characterized. In the present study, we examined the expression of A1, as well as the antioxidant manganous superoxide dismutase (MnSOD), in four human thyroid carcinoma cell lines, two human pancreatic carcinoma cell lines, and two human prostate carcinoma cell lines. A1 mRNA was expressed in all four thyroid carcinoma cell lines. TNF-alpha induced A1 in a time- and dose-dependent manner. In contrast, A1 mRNA was not detectable in the pancreatic and prostate carcinoma cell lines in the presence or absence of TNF-alpha. However, TNF-alpha induced manganous superoxide dismutase (MnSOD) mRNA in all the cell lines tested. Furthermore, an agonist antibody to the p55 TNF-alpha receptor induced A1, but the agonist antibody against p75 TNF-alpha receptor did not have this effect. The results indicate that A1 is expressed in human thyroid carcinoma cells and TNF-alpha induces A1 through the p55 TNF-alpha receptor-mediated pathway.