Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for androgen-insensitive prostate cancer cell invasion
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Xianxiang Xin1,2,*, Yinmin Gu1,*, Yang Chen3, Yuanjie Huang1, Zengnan Mo3 and Yanling Hu1,3,4
1Experimental Centre of Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China
2Commission for Discipline Inspection, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
3Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China
4Guangxi Colleges and Universities Key Laboratory of Biological Molecular Medicine Research, Guangxi Medical University, Nanning, Guangxi, China
*These authors have contributed equally to this work
Yanling Hu, email: email@example.com
Zengnan Mo, email: firstname.lastname@example.org
Keywords: prostate cancer, single nucleotide polymorphism, metastasis, androgen-insensitive
Received: June 11, 2016 Accepted: March 11, 2017 Published: April 04, 2017
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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