Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma
RET proto-oncogene encodes a receptor tyrosine kinase whose ligand is glial cell line-derived neurotrophic factor (GDNF), and its polymorphism at G691S juxtamembrane region (RETp) is a germline polymorphism. Cutaneous melanomas, particularly the desmoplastic subtype, are highly neurotropic; thus we...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738597/ https://www.ncbi.nlm.nih.gov/pubmed/19561646 http://dx.doi.org/10.1038/onc.2009.164 |
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author | Narita, N Tanemura, A Murali, R Scolyer, RA Huang, S Arigami, T Yanagita, S Chong, KK Thompson, JF Morton, DL Hoon, DS |
author_facet | Narita, N Tanemura, A Murali, R Scolyer, RA Huang, S Arigami, T Yanagita, S Chong, KK Thompson, JF Morton, DL Hoon, DS |
author_sort | Narita, N |
collection | PubMed |
description | RET proto-oncogene encodes a receptor tyrosine kinase whose ligand is glial cell line-derived neurotrophic factor (GDNF), and its polymorphism at G691S juxtamembrane region (RETp) is a germline polymorphism. Cutaneous melanomas, particularly the desmoplastic subtype, are highly neurotropic; thus we sought to determine the frequency of RETp in cutaneous melanoma and its functional responsiveness to GDNF. RETp was assessed in 71 non-desmoplastic cutaneous melanomas (non-DMs) and 70 desmoplastic melanomas (DMs). Melanoma cell lines with RETp, RET wild-type (RETwt), BRAF V600E mutation (BRAFmt) or BRAF wild-type (BRAFwt) were assessed for functional activity. RETp frequency was significantly higher in DMs (61%) than in non-DMs (31%, P<0.001). BRAFmt was detected in only 11% of DMs. GDNF stimulation significantly amplified cell proliferation, migration, and invasion in RETp, but not in RETwt melanoma cells. GDNF stimulation of RETp cell lines enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt of the RET-RAS-RAF-ERK and RET-phosphatidylinositol 3-kinase (PI3K)-Akt pathways, respectively. GDNF response of RETp cells in signal transduction and other functional studies were not affected by BRAFmt. The study demonstrates that RETp are frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression. |
format | Text |
id | pubmed-2738597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-27385972010-02-27 Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma Narita, N Tanemura, A Murali, R Scolyer, RA Huang, S Arigami, T Yanagita, S Chong, KK Thompson, JF Morton, DL Hoon, DS Oncogene Article RET proto-oncogene encodes a receptor tyrosine kinase whose ligand is glial cell line-derived neurotrophic factor (GDNF), and its polymorphism at G691S juxtamembrane region (RETp) is a germline polymorphism. Cutaneous melanomas, particularly the desmoplastic subtype, are highly neurotropic; thus we sought to determine the frequency of RETp in cutaneous melanoma and its functional responsiveness to GDNF. RETp was assessed in 71 non-desmoplastic cutaneous melanomas (non-DMs) and 70 desmoplastic melanomas (DMs). Melanoma cell lines with RETp, RET wild-type (RETwt), BRAF V600E mutation (BRAFmt) or BRAF wild-type (BRAFwt) were assessed for functional activity. RETp frequency was significantly higher in DMs (61%) than in non-DMs (31%, P<0.001). BRAFmt was detected in only 11% of DMs. GDNF stimulation significantly amplified cell proliferation, migration, and invasion in RETp, but not in RETwt melanoma cells. GDNF stimulation of RETp cell lines enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt of the RET-RAS-RAF-ERK and RET-phosphatidylinositol 3-kinase (PI3K)-Akt pathways, respectively. GDNF response of RETp cells in signal transduction and other functional studies were not affected by BRAFmt. The study demonstrates that RETp are frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression. 2009-06-29 2009-08-27 /pmc/articles/PMC2738597/ /pubmed/19561646 http://dx.doi.org/10.1038/onc.2009.164 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Narita, N Tanemura, A Murali, R Scolyer, RA Huang, S Arigami, T Yanagita, S Chong, KK Thompson, JF Morton, DL Hoon, DS Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma |
title | Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma |
title_full | Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma |
title_fullStr | Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma |
title_full_unstemmed | Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma |
title_short | Functional RET G691S Polymorphism in Cutaneous Malignant Melanoma |
title_sort | functional ret g691s polymorphism in cutaneous malignant melanoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738597/ https://www.ncbi.nlm.nih.gov/pubmed/19561646 http://dx.doi.org/10.1038/onc.2009.164 |
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