| RRC ID |
6833
|
| 著者 |
Ohshima Y, Yajima I, Takeda K, Iida M, Kumasaka M, Matsumoto Y, Kato M.
|
| タイトル |
c-RET molecule in malignant melanoma from oncogenic RET-carrying transgenic mice and human cell lines.
|
| ジャーナル |
PLoS One
|
| Abstract |
Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf) and Gdnf receptor alpha 1 (Gfra1) transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1) were higher than those in primary cultured normal human epithelial melanocytes (NHEM), while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT) sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma.
|
| 巻・号 |
5(4)
|
| ページ |
e10279
|
| 公開日 |
2010-4-21
|
| DOI |
10.1371/journal.pone.0010279
|
| PMID |
20422010
|
| PMC |
PMC2858158
|
| MeSH |
Animals
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation, Neoplastic*
Glial Cell Line-Derived Neurotrophic Factor / genetics*
Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics
Humans
Melanoma / chemistry
Melanoma / etiology*
Melanoma / genetics
Mice
Mice, Transgenic
Proto-Oncogene Proteins c-ret / genetics*
RNA, Messenger / analysis
|
| IF |
2.74
|
| 引用数 |
33
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
SK-Mel28(RCB1930) |
