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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-4-27
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-10220148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-10409632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-10637293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-11544105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-11815973,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-11956105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-12680189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-12748377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-14712226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-14871802,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-15340065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-15858113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-15870700,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-18089803,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-18652760,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-19276370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-19329283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-19561646,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-7814145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-7954839,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20422010-9778055
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GDNF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GFRA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Gdnf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ret,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:issn |
1932-6203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e10279
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pubmed:meshHeading |
pubmed-meshheading:20422010-Animals,
pubmed-meshheading:20422010-Cell Line, Tumor,
pubmed-meshheading:20422010-Cell Proliferation,
pubmed-meshheading:20422010-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20422010-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:20422010-Glial Cell Line-Derived Neurotrophic Factor Receptors,
pubmed-meshheading:20422010-Humans,
pubmed-meshheading:20422010-Melanoma,
pubmed-meshheading:20422010-Mice,
pubmed-meshheading:20422010-Mice, Transgenic,
pubmed-meshheading:20422010-Proto-Oncogene Proteins c-ret,
pubmed-meshheading:20422010-RNA, Messenger
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pubmed:year |
2010
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pubmed:articleTitle |
c-RET molecule in malignant melanoma from oncogenic RET-carrying transgenic mice and human cell lines.
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pubmed:affiliation |
Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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