Oncotarget

Research Papers:

Identification of differentially expressed genes in human breast cancer cells induced by 4-hydroxyltamoxifen and elucidation of their pathophysiological relevance and mechanisms

Qi Fang, Shuang Yao, Guanghua Luo and Xiaoying Zhang _

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Oncotarget. 2018; 9:2475-2501. https://doi.org/10.18632/oncotarget.23504

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Abstract

Qi Fang1, Shuang Yao2, Guanghua Luo2 and Xiaoying Zhang2

1Department of Breast Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China

2Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China

Correspondence to:

Xiaoying Zhang, email: zhangxy6689996@163.com

Guanghua Luo, email: shineroar@163.com

Keywords: breast cancer; MCF-7; 4-hydroxyl tamoxifen; STAT1; STAT2

Received: June 05, 2017    Accepted: December 13, 2017    Published: December 20, 2017

ABSTRACT

While tamoxifen (TAM) is used for treating estrogen receptor (ER)a-positive breast cancer patients, its anti-breast cancer mechanisms are not completely elucidated. This study aimed to examine effects of 4-hydroxyltamoxifen (4-OH-TAM) on ER-positive (ER+) breast cancer MCF-7 cell growth and gene expression profiles. MCF-7 cell growth was inhibited by 4-OH-TAM dose-dependently with IC50 of 29 μM. 332 genes were up-regulated while 320 genes were down-regulated. The mRNA levels of up-regulated genes including STAT1, STAT2, EIF2AK2, TGM2, DDX58, PARP9, SASH1, RBL2 and USP18 as well as down-regulated genes including CCDN1, S100A9, S100A8, ANXA1 and PGR were confirmed by quantitative real-time PCR (qRT-PCR). In human breast tumor tissues, mRNA levels of EIF2Ak2, USP18, DDX58, RBL2, STAT2, PGR, S1000A9, and CCND1 were significantly higher in ER+- than in ER--breast cancer tissues. The mRNA levels of EIF2AK2, TGM2, USP18, DDX58, PARP9, STAT2, STAT1, PGR and CCND1 were all significantly higher in ER+-tumor tissues than in their corresponding tumor-adjacent tissues. These genes, except PGR and CCND1 which were down-regulated, were also up-regulated in ER+ MCF-7 cells by 4-OH-TAM. Total 14 genes mentioned above are involved in regulation of cell proliferation, apoptosis, cell cycles, and estrogen and interferon signal pathways. Bioinformatics analysis also revealed other novel and important regulatory factors that are associated with these genes and involved in the mentioned functional processes. This study has paved a foundation for elucidating TAM anti-breast cancer mechanisms in E2/ER-dependent and independent pathways.


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