The exocrine pancreatic cell line AR42J is also known to display some neuroendocrine (NE) features. We have extended this fact by showing that AR42J cells express mRNA of chromogranin A (CgA), display immunoreactivity (IR) to CgA, and secrete its cleavage product pancreastatin. A sparse occurrence of typical NE secretion granules, together with only a faint IR to conventional NE markers, indicates that the NE cells are of a poorly differentiated type. CgA promoter reporter plasmid experiments showed that gastrin, epidermal growth factor, and phorbol 12-myristate 13-acetate, induce upregulation of CgA after 24 h. By RT-PCR, it was found that AR42J expresses all of the five subtypes of the somatostatin (SST) receptor (SSTR) family, except SSTR4. The existence of functional SSTRs was confirmed by showing that the SST analog octreotide could inhibit gastrin-induced proliferation. Thus, the AR42J cell line may function as a valuable experimental model to study the regulation of CgA and SSTRs in poorly differentiated NE tumor cells.