論文 - 詳細
| RRC ID | 44088 |
|---|---|
| 著者 | Yajima I, Kumasaka MY, Tamura H, Ohgami N, Kato M. |
| タイトル | Functional analysis of GNG2 in human malignant melanoma cells. |
| ジャーナル | J Dermatol Sci |
| 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. 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. |
| 巻・号 | 68(3) |
| ページ | 172-8 |
| 公開日 | 2012-12-1 |
| DOI | 10.1016/j.jdermsci.2012.09.009 |
| PII | S0923-1811(12)00273-3 |
| PMID | 23031273 |
| MeSH | Animals Cell Line, Tumor Cell Proliferation Endothelin-1 / metabolism GTP-Binding Proteins / antagonists & inhibitors GTP-Binding Proteins / genetics GTP-Binding Proteins / metabolism* Gene Knockdown Techniques Humans Melanoma / genetics Melanoma / metabolism* Melanoma / pathology Mice Mice, Nude Neoplasm Transplantation RNA, Small Interfering / genetics Receptor, Endothelin B / metabolism Signal Transduction Transplantation, Heterologous Up-Regulation |
| IF | 3.681 |
| 引用数 | 9 |
| WOS 分野 | DERMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | SK-MEL-28(RCB1930) |