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.
Department of Medicine, University of Toronto, Ontario, Canada.
J
J
Dong
S L
SL
Asa
D J
DJ
Drucker
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D005801:Genes, Homeobox; D018398:Homeodomain Proteins; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D016716:PC12 Cells; D010179:Pancreas / Q000166:cytology / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D004247:DNA