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400016重庆,重庆医科大学基础医学院生物化学与分子生物学教研室,分子医学与肿瘤研究中心
[ 刘智敏,E-mail: liuzm9999@aliyun.com LIU Zhimin, E-mail: liuzm9999@aliyun.com
收稿:2016-12-27,
修回:2017-03-24,
纸质出版:2017-09-15
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廖凌瑶, 戴宇婕, 赵婷婷, 等. 17β-雌二醇促进甲状腺乳头状癌细胞增殖、迁移及三叶草因子1分泌[J]. 第三军医大学学报, 2017,39(17):1715-1719.
Lingyao LIAO, Yujie DAI, Tingting ZHAO, et al. 17β-estradiol promotes proliferation, migration and TFF1 secretion in papillary thyroid cancer K-1 cells[J]. Journal of Third Military Medical University, 2017, 39(17): 1715-1719.
廖凌瑶, 戴宇婕, 赵婷婷, 等. 17β-雌二醇促进甲状腺乳头状癌细胞增殖、迁移及三叶草因子1分泌[J]. 第三军医大学学报, 2017,39(17):1715-1719. DOI: 10.16016/j.1000-5404.201612184.
Lingyao LIAO, Yujie DAI, Tingting ZHAO, et al. 17β-estradiol promotes proliferation, migration and TFF1 secretion in papillary thyroid cancer K-1 cells[J]. Journal of Third Military Medical University, 2017, 39(17): 1715-1719. DOI: 10.16016/j.1000-5404.201612184.
目的
2
研究17β-雌二醇(estradiol,E
2
)刺激甲状腺乳头状癌K-1细胞增殖、迁移及生长因子类似物人三叶草因子1(trefoil factor family 1,TFF1) 分泌及分子机制。
方法
2
ELISA检测E
2
、ERβ激动剂(propylpyrazoletriol,PPT)、ERβ激动剂(diarylpropionitrile,DPN)对K-1细胞TFF1分泌的影响,Western blot检测细胞中雌激素受体ERα、ERβ的表达量;设计合成ERα siRNA、ERβ siRNA后,转染K-1细胞,采用ELISA观察其对E
2
诱导的TFF1分泌的影响。染色体免疫共沉淀检测ERα、ERβ与TFF1基因启动子的相互作用;MTT检测E
2
对K-1细胞增殖的影响;Transwell检测E
2
对K-1细胞迁移的作用。
结果
2
E
2
处理后K-1细胞上清TFF1含量逐渐升高,24 h达到峰值,随后降低;PPT处理K-1细胞后TFF1含量增多,而DPN处理降低TFF1含量;转染ERα siRNA后细胞TFF1分泌量减少;而转染ERβ siRNA后分泌量升高。Western blot检测结果显示,K-1细胞中雌激素受体ERα表达高于ERβ。染色体免疫共沉淀结果显示,ERα能与TFF1基因启动子区域结合;MTT结果显示,E
2
处理促进K-1细胞增殖;Transwell检测结果显示,E
2
处理增强K-1细胞迁移。
结论
2
E
2
可以通过ERα促进K-1细胞中TFF1的表达及分泌,促进细胞增殖和迁移。
Objective
2
To investigate whether 17β-estradiol (E
2
) can stimulate the proliferation
migration
and secretion of trefoil factor family 1 (TFF1) in papillary thyroid cancer K-1 cells and explore the molecular mechanisms.
Methods
2
ELISA was used to detect the content of TFF1 in the supernatant of K-1 cells after the treatment of E
2
propylpyrazoletriol (PPT
ERα agonist) or diarylpropionitri
le (DPN
ERβ agonist). The expression of ERα and ERβ in the untreated cells was measured by Western blotting. ERα siRNA and ERβ siRNA by RNA interference were designed and synthesized
and the change of TFF1 was measured by ELISA again after the transfection. The interaction between TFF1 promoter and ER was evaluated by chromatin immunoprecipitation analysis (CHiP). The proliferation and migration were detected in the K-1 cells after E
2
treatment by MTT assay and Transwell chamber test respectively.
Results
2
After E
2
treatment
the TFF1 content in the supernatant of K-1 cells was increased gradually
reached peak at 24 h
and then declined slowly. PPT treatment enhanced the secretion of TFF1 but DPN decreased it in the K-1 cells. Transfection of ERα siRNA obliterated the inductive effect of E
2
on the secretion of TFF1
but that of ERβ siRNA increased the inductive effect in the K-1 cells. Western blotting showed that the expression level of ERα was higher than that of ERβ in the K-1 cells. ChIP results confirmed that ERα protein was bound to the promoter of TFF1 gene in K-1 cells. E
2
treatment promoted cell proliferation and improved cell migration in the K-1 cells.
Conclusion
2
E
2
induces the expression and secretion of TFF1 in K-1 cells through ERα-dependent manner
and thus promotes the proliferation and migration of the cells.
RAHBARI R, ZHANG L, KEBEBEW E. Thyroid cancer gender disparity[J]. Future Oncol, 2010, 6: 1771-1779. DOI: 10.2217/fon.10.127.
PERRY J K, KANNAN N, GRANDISON P M, et al. Are trefoil factors oncogenic?[J].Trends in Endocrinol Metab, 2008, 19 (2): 74-81. DOI: 10.1016/j.tem.2007.10.003.
PELDEN S, INSAWANG T, THUWAJIT C, et al. The trefoil factor 1 (TFF1) protein involved in doxorubicin?induced apoptosis resistance is upregulated by estrogen in breast cancer cells[J]. Oncol Rep, 2013, 30(3): 1518-1526. DOI: 10.3892/or.2013.2593.
LA ROSA P, PELLEGRINI M, TOTTA P, et al. Xenoestrogens alter estrogen receptor (ER) α intracellular levels[J]. PLoS One, 2014, 9(2): e88961. DOI: 10.1371/journal.pone.0088961.
GAO Q G, CHAN H Y, MAN C W, et al. Differential ERα-mediated rapid estrogenic actions of ginsenoside Rg1 and estren in human breast cancer MCF-7 cells[J]. J Steroid Biochem Mol Biol, 2014, 141: 104-112. DOI: 10.1016/j.jsbmb.2014.01.014.
METIVIER R, PENOT G, HUBNER M R, et al. Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter[J]. Cell, 2003, 115(6): 751-763.
莫小梅, 朱平, 刘智敏, 等. 17β-雌二醇对人甲状腺乳头状癌BCPAP细胞Hsp27表达的影响及作用机制[J].基础医学与临床, 2016, 36(10):1348-1353.DOI:10.16352/j.issn.1001-6325.2016.10.005.
MO X M, ZHU P, LIU Z M, et al.Effect of 17β-estradiol on the expression of Hsp27 by papillary thyroid cancer BCPAP cells and its mechanism[J].Basic Clin Med, 2016, 36(10):1348-1353.DOI:10.16352/j.issn.1001-6325.2016.10.005.
TAUPIN D, PODOLSKY D K. Trefoil factors: initiators of mucosal healing[J]. Nat Rev Mol Cell Biol, 2003, 4(9):721-732. DOI: 10.1038/nrm1203.
REGALO G. Trefoil factors: from ulceration to neoplasia[J]. Cell Mol Life Sci, 2005, 62(24): 2910-2915. DOI: 10.1007/s00018-005-5478-4.
EMAMI S. Trefoil factor family (TFF) peptides and cancer progression[J]. Peptides, 2004, 25(5): 885-898. DOI: 10.1016/j.peptides.2003.10.019.
BARON S, ESCANDE A, ALBÉROLA G, et al. Estrogen receptor α and the activating protein-1 complex cooperate during insulin-like growth factor-I-induced transcriptional activation of the pS2/TFF1 gene[J]. J Biol Chem, 2007, 282(16): 11732-11741. DOI:10.1074/jbc.M610079200.
BARKHEM T, HALDOSÉN L A, GUSTAFSSON J A, et al. PS2 gene expression in HepG2 cells: complex regulation through crosstalk between the estrogen receptor, an estrogen-responsive element, and the activator protein 1 response element[J]. Mol Pharmacol, 2002, 61(6): 1273-1283. DOI: 10.1124/mol.61.6.1273.
PLANEY S L, KUMAR R, ARNOTT J A. Estrogen receptors (ERα versus ERβ): friends or foes in human biology?[J].J Recept Signal Transduct Res, 2014, 34 (1): 1-5. DOI: 10.3109/10799893.2013.853188.
CHANG E C, FRASOR J, KOMM B, et al. Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells[J]. Endocrinology, 2006, 147 (10): 4831-4842. DOI:10.1210/en.2006-0563.
WILLIAMS C, EDVARDSSON K, LEWANDOWSKI S A, et al. A genome-wide study of the repressive effects of estrogen receptor beta on estrogen receptor alpha signaling in breast cancer cells[J]. Oncogene, 2008, 27 (7): 1019-1032. DOI: 10.1038/sj.onc.1210712.
BERRY M, NUNEZA M, Chambon P. Estrogen-responsive element of the human pS2 gene is an imperfectly palindromic sequence[J]. J Biol Chem, 1989, 86 (4): 1218-1222.
MATTHEWS J, WIHLÉN B, TUJAGUE M, et al. Estrogen receptor (ER) beta modulates ER alpha-mediated transcriptional activation by altering the recruitment of c-Fos and c-Jun to estrogen-responsive promoters[J]. Mol Endocrinol, 2006, 20(3): 534-543. DOI: 10.1210/me.2005-0140.
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