Increased expression of germinal center-associated nuclear protein (GANP) is associated with malignant transformation of melanocytes

J Dermatol Sci. 2006 Apr;42(1):55-63. doi: 10.1016/j.jdermsci.2005.12.007. Epub 2006 Jan 23.

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.

Objectives: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism*
  • Adolescent
  • Adult
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / metabolism*
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen / metabolism
  • Male
  • Melanocytes / metabolism*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Middle Aged
  • Minichromosome Maintenance Complex Component 3
  • Nevus, Pigmented / metabolism
  • Nevus, Pigmented / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger / metabolism

Substances

  • BCL6 protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • MCM3 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger
  • Acetyltransferases
  • MCM3AP protein, human
  • Minichromosome Maintenance Complex Component 3