Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1

The phenotypically distinct cell types of the islets of Langerhans express a number of different hormone genes in a regulated and cell-specific manner. Analysis of the molecular factors important for the control of insulin gene transcription has led to the identification of a number of insulin gene-binding proteins. The cDNAs for several of these proteins have been isolated, including isl-1, a LIM domain homeobox protein reported to be preferentially expressed in islet cells. We now report that isl-1 mRNA transcripts are present not only in islet cells, but also in pheochromocytoma (PC-12) cell lines. Isl-1 mRNA transcripts were also detected in several different regions of rat brain as well as in rat kidney. Analysis of the patterns of gene expression in rat islet cell lines and human pancreatic endocrine tumors demonstrated a variable relationship between the hormonal phenotype of the tumor and expression of the isl-1 and insulin genes. Immunocytochemical studies demonstrated both cytoplasmic and nuclear staining for isl-1 in human pancreatic endocrine tumors, in normal pancreatic A, B, D, and PP cells, and in distal tubular cells of the kidney. Isl-1 immunoreactivity was also widely distributed in neurons in both the central and peripheral nervous system, pituitary, and several human pituitary tumors and pheochromocytomas. The results of these studies implicate a potential role for isl-1 outside the endocrine pancreas in the nervous system and kidney.