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Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion

BACKGROUND: As one of the most common cancers in men, the pathogenesis of prostate cancer has been widely researched. Aberrant activation of the erb-b2 receptor tyrosine kinase 2 (ERBB2) has been found to play a critical role in metastatic prostate cancer. In our previous study, we demonstrated that...

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Autores principales: Xin, Xianxiang, Gu, Yinmin, Chen, Yang, Huang, Yuanjie, Mo, Zengnan, Hu, Yanling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464908/
https://www.ncbi.nlm.nih.gov/pubmed/28422721
http://dx.doi.org/10.18632/oncotarget.16807
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author Xin, Xianxiang
Gu, Yinmin
Chen, Yang
Huang, Yuanjie
Mo, Zengnan
Hu, Yanling
author_facet Xin, Xianxiang
Gu, Yinmin
Chen, Yang
Huang, Yuanjie
Mo, Zengnan
Hu, Yanling
author_sort Xin, Xianxiang
collection PubMed
description BACKGROUND: As one of the most common cancers in men, the pathogenesis of prostate cancer has been widely researched. Aberrant activation of the erb-b2 receptor tyrosine kinase 2 (ERBB2) has been found to play a critical role in metastatic prostate cancer. In our previous study, we demonstrated that rs61552325 (Pro1140Ala) located in ERBB2 is strongly correlated to prostate cancer. Therefore, we initially studied the effect of rs61552325 on androgen-independent prostate cancer cell metastasis. RESULTS: Bioinformatic results demonstrated that the mutant Pro1140Ala likely decrease the stability of the ERBB2 protein and its interactions. The mean migration rate after 6 h for PC3 minor variant cells which carried the G allele was 1.28-fold higher than major variant PC3 cells that carried the C allele (P = 0.016). The mean invasion rate of DU145 putative minor variant cells was 0.40 reducer than negative control cells (P = 5.9E-04). METHODS: rs61552325 major variant (C allele) and minor variant (G allele) were produced by site directed mutagenesis and transfected into DU145 and PC3 cells. A wound healing assay was performed to compare migration abilities between alleles. After knocking down endogenous ERBB2 and then expressing the rs61552325 minor variant, invasion abilities were evaluated with a transwell assay using DU145 and PC3 cells. CONCLUSIONS: Our data showed that the rs61552325 major variant decreases PC3 cell migration and its minor variant depresses DU145 cell invasion, suggesting that rs61552325 is likely an important change during prostate cancer invasion.
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spelling pubmed-54649082017-06-21 Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion Xin, Xianxiang Gu, Yinmin Chen, Yang Huang, Yuanjie Mo, Zengnan Hu, Yanling Oncotarget Research Paper BACKGROUND: As one of the most common cancers in men, the pathogenesis of prostate cancer has been widely researched. Aberrant activation of the erb-b2 receptor tyrosine kinase 2 (ERBB2) has been found to play a critical role in metastatic prostate cancer. In our previous study, we demonstrated that rs61552325 (Pro1140Ala) located in ERBB2 is strongly correlated to prostate cancer. Therefore, we initially studied the effect of rs61552325 on androgen-independent prostate cancer cell metastasis. RESULTS: Bioinformatic results demonstrated that the mutant Pro1140Ala likely decrease the stability of the ERBB2 protein and its interactions. The mean migration rate after 6 h for PC3 minor variant cells which carried the G allele was 1.28-fold higher than major variant PC3 cells that carried the C allele (P = 0.016). The mean invasion rate of DU145 putative minor variant cells was 0.40 reducer than negative control cells (P = 5.9E-04). METHODS: rs61552325 major variant (C allele) and minor variant (G allele) were produced by site directed mutagenesis and transfected into DU145 and PC3 cells. A wound healing assay was performed to compare migration abilities between alleles. After knocking down endogenous ERBB2 and then expressing the rs61552325 minor variant, invasion abilities were evaluated with a transwell assay using DU145 and PC3 cells. CONCLUSIONS: Our data showed that the rs61552325 major variant decreases PC3 cell migration and its minor variant depresses DU145 cell invasion, suggesting that rs61552325 is likely an important change during prostate cancer invasion. Impact Journals LLC 2017-04-04 /pmc/articles/PMC5464908/ /pubmed/28422721 http://dx.doi.org/10.18632/oncotarget.16807 Text en Copyright: © 2017 Xin et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Xin, Xianxiang
Gu, Yinmin
Chen, Yang
Huang, Yuanjie
Mo, Zengnan
Hu, Yanling
Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion
title Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion
title_full Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion
title_fullStr Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion
title_full_unstemmed Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion
title_short Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion
title_sort functional analysis implicating the snp rs61552325 in erbb2 as an effector for androgen-insensitive prostate cancer cell invasion
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464908/
https://www.ncbi.nlm.nih.gov/pubmed/28422721
http://dx.doi.org/10.18632/oncotarget.16807
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