title: B7-H4 expression in normal and diseased human islet β cells.
abstract: OBJECTIVE
  B7-H4 is a negative coregulatory molecule known to be involved in immune response. We study here B7-H4 expression and its possible role in diabetes and cancer development.
  
  
  METHODS
  Formalin-fixed, paraffin-processed pancreas samples from patients with type 1 diabetes (T1D), insulinoma, pancreatic ductal adenocarcinoma (PDAC), and normal organ donors were studied by bright-field and multifluorescence immunohistochemistry to examine B7-H4 expression and its colocalization with islet endocrine hormones. Quantitative RT-PCR and Western blot assay were used to examine B7-H4 mRNA and protein expression in the islet and exocrine tissues from normal donors and pancreatic cancer cell lines.
  
  
  RESULTS
  B7-H4 protein expression in islet β cells is decreased in T1D and PDAC, but increased in insulinoma patients when compared to normal controls; the changes in B7-H4 expression are concomitant with insulin expression on the islet β cells. The insulin/B7-H4 colocalization on the β cells, expressed in colocalization coefficient Pearson r, is also changed in these islets.
  
  
  CONCLUSIONS
  Our observation of altered B7-H4 expression, concomitant with insulin expression, in the pancreatic islets of T1D, PDAC, and insulinoma patients when compared to normal controls suggests that B7-H4 pathway might play an important role in maintenance of β-cell function, but its exact role remains to be explored.
authors: From the Departments of *Surgery and †Paediatrics, Faculty of Medicine, ‡Department of Experimental Therapeutics, Faculty of Pharmaceutical Sciences, University of British Columbia; and §British Columbia Cancer Agency; and ∥Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors: Susan S C
authors: SS
authors: Cheung
authors: Dawei
authors: D
authors: Ou
authors: Daniel L
authors: DL
authors: Metzger
authors: Mark
authors: M
authors: Meloche
authors: Ziliang
authors: Z
authors: Ao
authors: Sylvia S W
authors: SS
authors: Ng
authors: David
authors: D
authors: Owen
authors: Garth L
authors: GL
authors: Warnock
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human