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Menin represses malignant phenotypes of melanoma through regulating multiple pathways
Substantial genetic evidence suggests that chromosome 11q is involved in regulating initiation and progression of malignant melanomas. Mutations of the MEN1 gene, located in chromosome 11q13, predispose individuals to the multiple endocrine neoplasia type 1 (MEN1) familial syndrome. MEN1 patients de...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822947/ https://www.ncbi.nlm.nih.gov/pubmed/21129151 http://dx.doi.org/10.1111/j.1582-4934.2010.01222.x |
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author | Gao, Shu-Bin Feng, Zi-Jie Xu, Bin Chen, Yan Zheng, Hong-Hua Yin, Ping Hua, Xianxin Jin, Guang-Hui |
author_facet | Gao, Shu-Bin Feng, Zi-Jie Xu, Bin Chen, Yan Zheng, Hong-Hua Yin, Ping Hua, Xianxin Jin, Guang-Hui |
author_sort | Gao, Shu-Bin |
collection | PubMed |
description | Substantial genetic evidence suggests that chromosome 11q is involved in regulating initiation and progression of malignant melanomas. Mutations of the MEN1 gene, located in chromosome 11q13, predispose individuals to the multiple endocrine neoplasia type 1 (MEN1) familial syndrome. MEN1 patients develop primary malignant melanoma, suggesting a potential link between MEN1 syndrome and development of melanomas, but the precise molecular mechanism is poorly understood. Here we show that the MEN1 gene suppresses malignant phenotypes of melanoma cells through multiple signalling pathways. Ectopic expression of menin, the product of MEN1 gene, significantly inhibited melanoma cell proliferation and migration in vitro and in vivo. The inhibition was partly achieved through suppressing expression of growth factor pleiotrophin (PTN) and receptor protein tyrosine phosphatase (RPTP) β/ζ, accompanied with the reduced expression of phosphatidylinositol 3-kinase (pI3K) and decreased phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase (ERK1/2). Interestingly, reduced expression of menin was associated with hypermethylation of the CpG islands of the MEN1 promoter in melanoma cells. Taken together, these findings suggest a previously unappreciated function for menin in suppressing malignant phenotypes of melanomas and unravel a novel mechanism involving in regulating PTN signalling by menin in development and progression of melanomas. |
format | Online Article Text |
id | pubmed-3822947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-38229472015-04-06 Menin represses malignant phenotypes of melanoma through regulating multiple pathways Gao, Shu-Bin Feng, Zi-Jie Xu, Bin Chen, Yan Zheng, Hong-Hua Yin, Ping Hua, Xianxin Jin, Guang-Hui J Cell Mol Med Original Articles Substantial genetic evidence suggests that chromosome 11q is involved in regulating initiation and progression of malignant melanomas. Mutations of the MEN1 gene, located in chromosome 11q13, predispose individuals to the multiple endocrine neoplasia type 1 (MEN1) familial syndrome. MEN1 patients develop primary malignant melanoma, suggesting a potential link between MEN1 syndrome and development of melanomas, but the precise molecular mechanism is poorly understood. Here we show that the MEN1 gene suppresses malignant phenotypes of melanoma cells through multiple signalling pathways. Ectopic expression of menin, the product of MEN1 gene, significantly inhibited melanoma cell proliferation and migration in vitro and in vivo. The inhibition was partly achieved through suppressing expression of growth factor pleiotrophin (PTN) and receptor protein tyrosine phosphatase (RPTP) β/ζ, accompanied with the reduced expression of phosphatidylinositol 3-kinase (pI3K) and decreased phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase (ERK1/2). Interestingly, reduced expression of menin was associated with hypermethylation of the CpG islands of the MEN1 promoter in melanoma cells. Taken together, these findings suggest a previously unappreciated function for menin in suppressing malignant phenotypes of melanomas and unravel a novel mechanism involving in regulating PTN signalling by menin in development and progression of melanomas. Blackwell Publishing Ltd 2011-11 2011-10-24 /pmc/articles/PMC3822947/ /pubmed/21129151 http://dx.doi.org/10.1111/j.1582-4934.2010.01222.x Text en © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd |
spellingShingle | Original Articles Gao, Shu-Bin Feng, Zi-Jie Xu, Bin Chen, Yan Zheng, Hong-Hua Yin, Ping Hua, Xianxin Jin, Guang-Hui Menin represses malignant phenotypes of melanoma through regulating multiple pathways |
title | Menin represses malignant phenotypes of melanoma through regulating multiple pathways |
title_full | Menin represses malignant phenotypes of melanoma through regulating multiple pathways |
title_fullStr | Menin represses malignant phenotypes of melanoma through regulating multiple pathways |
title_full_unstemmed | Menin represses malignant phenotypes of melanoma through regulating multiple pathways |
title_short | Menin represses malignant phenotypes of melanoma through regulating multiple pathways |
title_sort | menin represses malignant phenotypes of melanoma through regulating multiple pathways |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822947/ https://www.ncbi.nlm.nih.gov/pubmed/21129151 http://dx.doi.org/10.1111/j.1582-4934.2010.01222.x |
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