p22/PACAP response gene-1 (PRG1) is a novel rat early response gene expressed during induction of proliferation and stress response. In humans, a homolog of p22/PRG1, designated IEX-1/DIF-2, exists, yet the exact function of this gene remains elusive. To characterize the expression of p22/PRG1 in human cancers, we analyzed the expression of p22/PRG1 in the human pancreatic carcinoma cell lines 818-4, PT45, and PancTu1. Serum or growth factors, like epidermal growth factor (EGF) and hepatocyte growth factor (HGF), rapidly and transiently induced transcription of p22/PRG1 in these cells, correlating with the mitogenic response. Treatment with TNF-alpha was followed by a rapid increase of p22/PRG1 messenger RNA (mRNA) levels in PT45 and Panc-Tul cells, which proliferate in the presence of TNF-alpha, but not in 818-4 cells, which are growth-inhibited when treated with TNF-alpha. Our findings suggest that human p22/PRG1 is expressed in various pancreatic carcinoma cells as a growth-associated early response gene.