Functional analysis of GNG2 in human malignant melanoma cells

Ichiro Yajima, Mayuko Y. Kumasaka, Haruka Tamura, Nobutaka Ohgami, Masashi Kato

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 p21Cip/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 p21Cip/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. Conclusion: 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.

Original languageEnglish
Pages (from-to)172-178
Number of pages7
JournalJournal of Dermatological Science
Volume68
Issue number3
DOIs
Publication statusPublished - 2012 Dec 1

Keywords

  • G-protein
  • Gamma subunit
  • Malignant melanoma
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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