title: Functional analysis of GNG2 in human malignant melanoma cells.
abstract: BACKGROUND
  Previous studies have revealed that heterotrimeric G protein is composed of a Gα-subunit and a Gβγ-dimer and is correlated with c-Src and AKT activities. Our recent study showed reduced G protein γ2 subunit (Gng2/GNG2) expression levels in malignant melanoma cells compared with those in benign melanocytic cells in both mice and humans. At present, however, there is no evidence showing an effect of Gng2/GNG2 alone on cancer biology.
  
  
  OBJECTIVE
  The purpose of this study was to examine the biological significance of GNG2 in human malignant melanoma cells.
  
  
  METHODS
  Levels of proliferation and activities of signal transduction molecules were examined in both GNG2-overexpressed and -depleted human malignant melanoma cells.
  
  
  RESULTS
  Proliferation of GNG2-overexpressed SK-Mel28 human malignant melanoma cells was suppressed with decreased c-SRC and AKT activities and increased p21(Cip/WAF1) expression level in vitro. In contrast, proliferation of GNG2-depleted A375P human malignant melanoma cells was enhanced with increased c-SRC and AKT activities and decreased p21(Cip/WAF1) expression level in vitro. In the in vivo experiment, the mean tumor size of GNG2-overexpressed SK-Mel28 cells was less than 1/45th of that of control SK-Mel28 cells in nude mice at 95 days after inoculation.
  
  
  CONCLUSIONS
  We demonstrated for the first time that increased protein expression level of GNG2 alone inhibits proliferation of malignant melanoma cells in vitro and in vivo, suggesting that GNG2 could be a novel molecular target for malignant melanoma therapy.
authors.affiliation: Unit of the Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.forename: Haruka
authors.initials: H
authors.lastname: Tamura
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohgami
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019332:Endothelin-1 / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D044023:Receptor, Endothelin B / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; C410342:GNG2 protein, human; D034741:RNA, Small Interfering; D044023:Receptor, Endothelin B; D019204:GTP-Binding Proteins