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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...

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Autores principales: Gao, Shu-Bin, Feng, Zi-Jie, Xu, Bin, Chen, Yan, Zheng, Hong-Hua, Yin, Ping, Hua, Xianxin, Jin, Guang-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2011
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.
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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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