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

ABSTRACT: 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.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).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.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.

SUBMITTER: Xin X

PROVIDER: S-EPMC5464908 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Xin Xianxiang X Gu Yinmin Y Chen Yang Y Huang Yuanjie Y Mo Zengnan Z Hu Yanling Y

Oncotarget 20170501 20

<h4>Background</h4>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 metast ...[more]

PMID: 28422721

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Project description:Epigenetic changes have been suggested to drive prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to identify novel epigenetics-related genes in PCa tissues, and to examine their expression in metastatic PCa cell lines. We analyzed the expression of epigenetics-related genes via a clustering analysis based on gene function in moderately and poorly differentiated PCa glands compared to normal glands of the peripheral zone (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays. Our analysis identified 12 epigenetics-related genes with a more than 2-fold increase or decrease in expression and a p-value <0.01. In modera-tely differentiated tumors compared to normal glands of the peripheral zone, we found the genes, TDRD1, IGF2, DICER1, ADARB1, HILS1, GLMN and TRIM27, to be upregulated, whereas TNRC6A and DGCR8 were found to be downregulated. In poorly differentiated tumors, we found TDRD1, ADARB and RBM3 to be upregulated, whereas DGCR8, PIWIL2 and BC069781 were downregulated. Our analysis of the expression level for each gene in the metastatic androgen-sensitive VCaP and LNCaP, and -insensitive PC3 and DU-145 PCa cell lines revealed differences in expression among the cell lines which may reflect the different biological properties of each cell line, and the potential role of each gene at different metastatic sites. The novel epigenetics-related genes that we identified in primary PCa tissues may provide further insight into the role that epigenetic changes play in PCa. Moreover, some of the genes that we identified may play important roles in primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up studies are required to investigate the functional role and the role that the expression of these genes play in the outcome and progression of PCa using tissue microarrays.

Dataset Information

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

Publications

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

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