NKX6.1 [MD254]

Members of the NKX family of homeodomain proteins are key regulators of growth and development in several tissues, including brain, heart and pancreas. During neural development, sonic hedgehog (Shh) is known to control cell fate and mitogenesis, which is correlated with Shh dose-dependent expression of several genes, including NKX6.1. Specifically, NKX6.1 is responsible for cellular differentiation in the ventral neural tube and spinal meninges in response to Shh. In the pancreas, NKX6.1 is exclusively expressed in the islets of Langerhans in differentiating and mature B cells, which produce Insulin. The presence of PDX1 is required for the expression of NKX6.1 as well as other pancreatic B cell specific genes, including Insulin, Glut2 and IAPP. Subsequently, NKX6.1 binds to the DNA consensus sequence, TTAATTAC, to direct the repression of specific genes in B cells. NKX6.1 is highly expressed in pancreatic and duodenal well-differentiated neuroendocrine tumors (WDNETS) and in metastatic WDNETS, is a highly specific marker of tumors of pancreatic origin. It has thus been suggested that NKX6.1 is a useful inclusion into IHC panels for identifying primary sites of WDNETS.