Oncotarget

Research Papers:

Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer

Xin Men, Jun Ma, Tong Wu, Junyi Pu, Shaojia Wen, Jianfeng Shen, Xun Wang, Yamin Wang, Chao Chen and Penggao Dai _

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Oncotarget. 2018; 9:4074-4089. https://doi.org/10.18632/oncotarget.23694

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Abstract

Xin Men1, Jun Ma1, Tong Wu1, Junyi Pu1, Shaojia Wen1, Jianfeng Shen1, Xun Wang1, Yamin Wang1, Chao Chen1 and Penggao Dai1

1National Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi’an, PR China

Correspondence to:

Penggao Dai, email: [email protected]

Chao Chen, email: [email protected]

Keywords: tamoxifen; resistance; transcriptome; RNA-seq; breast cancer

Received: May 24, 2017    Accepted: December 15, 2017    Published: December 26, 2017

ABSTRACT

Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and compared the gene expression profiles between the MCF-7 mamma carcinoma cell line and the TAM-resistant cell line TAMR/MCF-7, 52 significant differential expression genes (DEGs) were identified including SLIT2, ROBO, LHX, KLF, VEGFC, BAMBI, LAMA1, FLT4, PNMT, DHRS2, MAOA and ALDH. The DEGs were annotated in the GO, COG and KEGG databases. Annotation of the function of the DEGs in the KEGG database revealed the top three pathways enriched with the most DEGs, including pathways in cancer, the PI3K-AKT pathway, and focal adhesion. Then we compared the gene expression profiles between the Clinical progressive disease (PD) and the complete response (CR) from the cancer genome altas (TCGA). 10 common DEGs were identified through combining the clinical and cellular analysis results. Protein-protein interaction network was applied to analyze the association of ER signal pathway with the 10 DEGs. 3 significant genes (GFRA3, NPY1R and PTPRN2) were closely related to ER related pathway. These significant DEGs regulated many biological activities such as cell proliferation and survival, motility and migration, and tumor cell invasion. The interactions between these DEGs and drug resistance phenomenon need to be further elucidated at a functional level in further studies. Based on our findings, we believed that these DEGs could be therapeutic targets, which can be explored to develop new treatment options.


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