FA1 IMMUNOREACTIVITY IN ENDOCRINE TUMORS AND DURING DEVELOPMENT OF THE HUMAN FETAL PANCREAS - NEGATIVE CORRELATION WITH GLUCAGON EXPRESSION

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growt h factor (EGF)-like repeats. It is closely similar to the protein tran slated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Droso phila homeotic proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determin ing cell fate choices during differentiation. We now report that FA1 i mmunoreactivity is present in a number of neuroectodermally derived tu mours as well as in pancreatic endocrine tumours. A negative correlati on between FA1 and glucagon immunoreactants in these rumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic develop ment. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing development, gradually disappeared from these cells and became restricted to insul in-producing beta cells. Throughout development FA1 was not detected i n endocrine glucagon, somatostatin or pancreatic polypeptide cells. Mo reover, developing insulin cells that coexpressed glucagon were negati ve for FA1. Thus, there was a negative correlation between FA1 and glu cagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of F A1 in islet cell differentiation.