外源性17β-雌二醇促进HER2阳性乳腺癌细胞的侵袭和增殖

摘要
图/表
参考文献
相关文章 (0)

全文: PDF (4485 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：研究外源性雌激素是否对乳腺癌中人表皮生长因子受体2（HER2）阳性乳腺癌细胞产生作用。方法：分别以乳腺癌细胞SKBR3和MCF-7为材料，选择17β-雌二醇（E2）为外源雌激素，配制10-5、10-6、10-7、10-8、10-9、10-10 mol/L的6种浓度培养环境，每种浓度培养时间设置24、48、72 h 3个梯度。检测HER2、ERα等标志物表达水平变化，分析E2对HER2阳性乳腺癌细胞增殖能力及侵袭性的影响。结果：在MCF-7中处理组HER2、ERα的转录水平都明显高于阴性对照组。在SKBR3细胞中仅HER2转录水平明显高于阴性对照组（P＜0.05）。在蛋白水平SKBR3中HER2蛋白表达量增加（P＜0.05）；而在MCF-7中，ERα蛋白表达量随着时间的延长而增加，HER2几乎检测不到。在细胞增殖方面，MCF-7和SKBR3均随着E2浓度的上升细胞增殖率上升，差异有统计学意义（P＜0.05）。而在侵袭性方面，MCF-7的侵袭性在72 h时较空白对照组增强（P＜0.05），SKBR3侵袭性在24 h和48 h时较空白对照组增强（P＜0.05），但是自身随浓度变化的规律不明显。结论：外源性雌激素对HER2阳性乳腺癌细胞的侵袭和增殖有促进作用。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	徐宝宝
	姜阳
	王金丹
	李昔琪
	何媛媛
	阮青青
	柳鹏程
	高国辉
	金龙金

关键词 ： 17β-E2；受体, 表皮生长因子；受体, 雌激素；基因表达；乳腺肿瘤；细胞增殖；肿瘤侵润

Abstract：Objective: To investigate the correlation between exogenous estrogens (EEs) and the development risk of HER2 positive breast cancer cells. Methods: We treated HER2-positive and ERα-negative cells SKBR3, ERα-positive and HER2-negative cells MCF-7 with 17β-estradiol. The six different concentrations of 17β-estradiol were 10-5, 10-6, 10-7, 10-8, 10-9, 10-10 mol/L. For each concentration condition, there were three time dose such as 24 h, 48 h, 72 h. The expression levels of HER2 and ERα were observed as the key positive marker. And then cell invasion and cell proliferation of breast cancer cells were analysed for MCF-7 and SKBR3 under 17β-estradiol treatment. Results: It showed that the transcriptional levels of HER2 and ERα were upregulated in MCF7 cells under all 18 different conditions. However, only the transcriptional levels of HER2 was upregulated in all 18 different conditions in HER2-positive and ERα-negative SKBR3. At protein expression levels, HER2 in SKBR3 cells and ERα in MCF-7 cells were expressed apparently after the breast cancer cells were stimulated by 17β-estradiol under all different conditions. Simultaneously,the proliferation of MCF-7 and SKBR3 were promoted obviously. With the higher concentration of 17β-estradiol treatment the proliferative activity of these two breast cancer cells were promoted much more obviously. As for the invasion of the breast cancer cells, MCF-7 was increased after 72 h, and SKBR3 was increased after 24 h and 48 h. Whereas the invasion of SKBR3 and MCF-7 were not up or down regulated evidently with the change of concentrations and time. Conclusion: In a word, the expression levels of HER2 in HER2 positive breast cancer cells SKBR3 are upregulated under different 17β-estradiol treatment conditions. Furthermore, the invasion and proliferation of HER2 positive breast cancer cells SKBR3 are promoted under exogenous estrogens 17β-estradiol treatment.

Key words： 17β-estradiol receptor, epidermal growth factor receptor, estrogen gene expression breast neoplasms cell proliferation neoplasm invasiveness

收稿日期: 2016-09-19

基金资助:国家自然科学基金资助项目（81572580）；浙江省自然科学基金资助项目（Y2110623）；浙江省医药卫生计划项目（2012KYA128）。

通讯作者: 金龙金，教授，硕士生导师，Email：ggh1227@126.com。

作者简介: 徐宝宝（1988-），男，陕西渭南人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I5/329

[1] TOVEY S M, REEVES J R, STANTON P, et al. Low expression of HER2 protein in breast cancer is biologically significant[J]. J Pathol, 2006, 210(3): 358-362.
[2] LANDIS M D, SEACHRIST D D, ABDUL-KARIM F W, et al. Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors[J]. Oncogene, 2006, 25(23): 3325-3334.
[3] KEY T, APPLEBY P, BARNES I, et al. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies[J]. J Natl Cancer Inst, 2002, 94(8): 606-616.
[4] PIKE M C, SPICER D V, DAHMOUSH L, et al. Estrogens,progestogens, normal breast cell proliferation, and breast cancer risk[J]. Epidemiol Rev, 1993, 15(1):17-35.
[5] KOSSMAN D A, WILLIAMS N I, DOMCHEK S M, et al. Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer[J]. J Appl Physiol, 2011, 111(6): 1687-1693.
[6] ANDRECHEK E R. HER2/Neu tumorigenesis and metastasis is regulated by E2F activator transcription factors[J]. Oncogene, 2015, 34(2): 217-225.
[7] PALMA G, FRASCI G, CHIRICO A, et al. Triple negative breast cancer looking for the missing link between biology and treatments[J]. Oncotarget, 2015, 6(29): 26560-26574.
[8] ZIEGLER R G, FUHRMAN B J, MOORE S C, et al. Epide-miologic studies of estrogen metabolism and breast cancer [J]. Steroids, 2015, 99(Pt A): 67-75.
[9] MASKARINEC G, BECKFORD F, MORIMOTO Y, et al. Association of estrogen measurements in serum and urine of premenopausal women[J]. Biomark Med, 2015, 9(5): 417-424.
[10] GREEN S, WALTER P, KUMAR V, et al. Human oestrogen receptor cDNA: sequence, expression and homology to verb-A[J]. Nature, 1986, 320(6058): 134-139.
[11] MADAK-ERDOGAN Z, GONG P, KATZENELLENBOGEN B S, et al. Differential utilization of nuclear and extranuclear receptor signaling pathways in the actions of estrogens, SERMs, and a tissue-selective estrogen complex (TSEC)[J]. J Steroid Biochem Mol Biol, 2016, 158: 198-206.
[12] COWLEY S M, HOARE S, MOSSELMAN S, et al. Estrogen receptors alpha and beta form heterodimers on DNA[J]. J Biol Chem, 1997, 272(32): 19858-19862.
[13] KIM J, SZINTE J S, BOULWARE M I, et al. 17β-estradiol and agonism of G-protein-coupled estrogen receptor enhance hippocampal memory via different cell-signaling mechanisms[J]. J Neurosci, 2016, 36(11): 3309-3321.
[14] ZHOU X, WANG S, WANG Z, et al. Estrogen regulates Hippo signaling via GPER in breast cancer[J]. J Clin Invest, 2015, 125(5): 2123-2135.
[15] ČÁSLAVSKÝ J, KLÍMOVÁ Z, VOMASTEK T, et al. ERK and RSK regulate distinct steps of a cellular program that induces transition from multicellular epithelium to single cell phenotype[J]. Cell Signal, 2013, 25(12): 2743-2751.
[16] SHI C, ZHU X, WANG J, et al. Estrogen receptor α promotes non-amyloidogenic processing of platelet amyloid precursor protein via the MAPK/ERK pathway[J]. J Steroid Biochem Mol Biol, 2014, 144(Pt B): 280-285.
[17] KIROUAC D C, DU J, LAHDENRANTA J, et al. HER2+ cancer cell dependence on PI3K vs. MAPK signaling axes is determined by expression of EGFR, ERBB3 and CDKN1B [J]. PLoS Comput Biol, 2016, 12(4): e1004827.
[18] ZHANG X, DENG H, WANG Z Y. Estrogen activation of the mitogen-activated protein kinase is mediated by ER-α36 in ER-positive breast cancer cells[J]. J Steroid Biochem Mol Biol, 2014, 143: 434-443.
[19] CRONAN M R, NAKAMURA K, JOHNSON NL, et al. Defining MAP3 kinases required for MDA-MB-231 cell tumor growth and metastasis[J]. Oncogene, 2012, 31(34): 3889-3900.
[20] MONTERO J C, OCAÑA A, ABAD M, et al. Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target[J]. PLoS One, 2009, 4(5): e5565.