|本期目录/Table of Contents|

[1]周岩,宋伟杰,张飞,等.人附睾蛋白4在乳腺癌发生发展中的机制研究[J].天津医科大学学报,2015,21(06):466-468.
 ZHOU Yan,SONG Wei-jie,ZHANG Fei,et al.Mechanism of human epididymis protein 4 in development and progression of breast cancer[J].Journal of Tianjin Medical University,2015,21(06):466-468.
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人附睾蛋白4在乳腺癌发生发展中的机制研究(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
21
期数:
2015年06期
页码:
466-468
栏目:
基础医学
出版日期:
2015-11-20

文章信息/Info

Title:
Mechanism of human epididymis protein 4 in development and progression of breast cancer
文章编号:
1006-8147(2015)06-0466-03
作者:
周岩1宋伟杰1张飞1冀为1田然1牛瑞芳1黎小沛2
(1.天津医科大学肿瘤医院,国家肿瘤临床医学研究中心,天津市“肿瘤防治“重点实验室,肿瘤研究所公共实验室,天津 300060;2 天津医科大学基础医学院,天津 300070)
Author(s):

ZHOU Yan1 SONG Wei-jie1 ZHANG Fei1 JI Wei1 TIAN Ran1 NIU Rui-fang1 LI Xiao-pei2

?

(1 Department of Public Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin 300060,China; 2 Basic Medical College,Tianjin Medical University, Tianjin 300070,China)
关键词:
人附睾蛋白4乳腺癌增殖凋亡
Keywords:
human epididymis protein 4 breast cancerproliferation apoptosis
分类号:
R737.9
DOI:
-
文献标志码:
A
摘要:
?目的: 探讨人附睾蛋白4(HE4)在乳腺癌发生发展中的机制研究。方法:采用实时荧光定量PCR(RT-qPCR)检测15例原发乳腺癌组织及其配对的癌旁正常组织中HE4 mRNA的表达水平。 RT-qPCR和Western blot 检测常见乳腺(癌)细胞系中HE4 mRNA和蛋白表达水平。通过RNA干扰技术沉默HE4高表达的乳腺癌SKBR3细胞中HE4表达,通过CCK8和克隆形成实验分析沉默HE4表达对SKBR3细胞细胞增殖的影响。 流式细胞术检测沉默HE4表达对SKBR3细胞凋亡的影响。 Western blot检测沉默HE4表达对Erk和Akt磷酸化水平的影响。结果:HE4 mRNA 在乳腺癌组织中高表达;沉默HE4表达抑制乳腺癌细胞SKBR3细胞增殖能力,并促进其凋亡,Erk和Akt蛋白磷酸化水平降低。结论:HE4通过影响Erk和Akt信号通路促进乳腺癌发生发展。
Abstract:
Objective:To explore the mechanism of human epididymis protein 4(HE4) in breast cancer development and progression. Methods: Reverse transcription quantitative PCR (RT-qPCR) was used to detect the HE4 mRNA expression levels in primary breast cancer tissues and the paired adjacent normal tissues. The HE4 mRNA and protein expression was also detected in breast epithelial cell lines by RT-qPCR and western blot, respectively. The RNAi was used to knock down the HE4 expression in HE4 high expression level cell line SKBR3, CCK8 and colony formation assays were performed to analyze the proliferation ability. Flow cytometry was applied to detect the apoptotic cells in HE4-depleted cells. The phosphorylation expression levels of Erk and Akt was evaluated by western blot. Results: The HE4 mRNA was up-regulated in primary breast cancer tissues compared with the adjacent normal breast tissues. Depletion of HE4 expression suppressed the proliferation and promoted the apoptosis in SKBR3 breast cancer cell line. Furthermore, the phosphorylation expression levels of Erk and Akt were reduced in HE4-depleted SKBR3 cells. Conclusion: HE4 promotes breast cancer development and progression through Erk and Akt signaling.

参考文献/References:

[1]Bingle L, Singleton V, Bingle C D. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms[J]. Oncogene, 2002,21(17):2768
[2]Clauss A, Lilja H, Lundwall A. A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein[J]. Biochem J, 2002,368(Pt 1):233
[3]Galgano M T, Hampton G M, Frierson H F. Comprehensive analysis of HE4 expression in normal and malignant human tissues[J]. Mod Pathol, 2006,19(6):847
[4]Zou S L, Chang X H, Ye X, et al. Effect of human epididymis protein 4 gene silencing on the malignant phenotype in ovarian Cancer[J]. Chin Med J (Engl), 2011,124(19):3133
[5]Li J, Chen H, Mariani A, et al. HE4 (WFDC2) promotes tumor growth in endometrial cancer cell lines[J]. Int J Mol Sci, 2013,14(3):6026
[6]Zhuang H, Tan M, Liu J, et al. Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells[J]. Mol Cancer, 2014,13:243
[7]Guo Y D, Wang J H, Lu H, et al. The human epididymis protein 4 acts as a prognostic factor and promotes progression of gastric cancer[J]. Tumour Biol, 2015,36(4):2457
[8]Wang X, Fan Y, Wang J, et al. Evaluating the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer[J]. Tumour Biol, 2014,35(7):6847
[9]Hellstr?m I, Raycraft J, Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma[J]. Cancer Res, 2003,63(13):3695
[10]Clauss A, Ng V, Liu J, et al. Overexpression of elafin in ovarian carcinoma is driven by genomic gains and activation of the nuclear factor kappaB pathway and is associated with poor overall survival[J]. Neoplasia, 2010,12(2):161
[11]Wang H, Zhu L, Gao J, et al. Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells[J]. Oncol Rep, 2015,33(1):403
[12]Mccubrey J A, Steelman L S, Chappell W H, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance[J]. Oncotarget, 2012,3(10):1068

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备注/Memo

备注/Memo:

基金项目 天津市应用基础及前沿技术研究计划项目基金资助(10JCYBJC14400)

作者简介 周岩(1985-),女,硕士在读,研究方向:生物医学工程;

通信作者 :黎小沛,E-mail:xpli@tijmu.edu.cn

更新日期/Last Update: 2015-11-27