title: Increased expression of germinal center-associated nuclear protein (GANP) is associated with malignant transformation of melanocytes.
abstract: BACKGROUND
  Germinal center-associated nuclear protein (GANP) is a newly cloned molecule that is up-regulated in the germinal center B cells. Although GANP functions in the regulation of DNA repair during replication and survival of B cells, little is known about its expression in melanocytic cells.
  
  
  OBJECTIVE
  To investigate whether GANP and phosphorylated-GANP (P-GANP) are expressed in cultured human melanocytes and melanoma cells and in benign and malignant melanocytic lesions. In addition, we aim to determine whether GANP and P-GANP are associated with malignant transformation of melanocytic lineage.
  
  
  METHODS
  GANP and P-GANP expression in cultured melanocytic cells was analyzed by immunostaining and in vitro kinase assay. GANP and P-GANP expression in melanocytic lesions was analyzed by immunohistochemistry.
  
  
  RESULTS
  GANP and P-GANP were up-regulated in cultured melanoma cells compared to melanocytes. GANP and P-GANP were restricted to nucleus of melanocytes but co-expressed in cytoplasm of melanoma cells. On the other hand, GANP and P-GANP were widely expressed at various levels in melanocytic nevi and melanoma lesions with nuclear and cytoplasmic staining pattern. Melanoma cells showed a stronger intensity of GANP and P-GANP than melanocytic nevus cells, however the staining intensity in primary melanoma lesions was not associated with any clinicopathological variables. Cytoplasmic GANP and P-GANP expression was associated with MCM3 and Ki67 expression.
  
  
  CONCLUSIONS
  These data suggest, for the first time, that GANP and P-GANP are up-regulated in cultured melanoma cells compared to melanocytes and also they are widely expressed in benign and malignant melanocytic tumor cells.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kageshita
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kuwahara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
authors.forename: Donglai
authors.initials: D
authors.lastname: Ma
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Ono
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D064126:Minichromosome Maintenance Complex Component 3; D009508:Nevus, Pigmented / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C084103:BCL6 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C066470:MCM3 protein, human; D009687:Nuclear Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D000123:Acetyltransferases; C406825:MCM3AP protein, human; D064126:Minichromosome Maintenance Complex Component 3