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甲状腺激素——三碘甲状腺原氨酸——对人近端肾小管细胞系（HK2）和肾癌细胞系（Caki - 2、Caki - 1）的增殖具有相反作用——E2F4、E2F5以及p107、p130的作用

Thyroid hormone - triiodothyronine - has contrary effect on proliferation of human proximal tubules cell line (HK2) and renal cancer cell lines (Caki-2, Caki-1) - role of E2F4, E2F5 and p107, p130.

作者信息

Poplawski Piotr, Nauman Alicja

机构信息

Department of Biochemistry and Molecular Biology, The Medical Centre of Postgraduate Education, Warsaw, Poland.

出版信息

Thyroid Res. 2008 Oct 13;1(1):5. doi: 10.1186/1756-6614-1-5.

DOI:10.1186/1756-6614-1-5
PMID:19014670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2583984/
Abstract

BACKGROUND

Triiodothyronine regulates proliferation acting as stimulator or inhibitor. E2F4 and E2F5 in complexes with pocket proteins p107 or p130 stop cells in G1, repressing transcription of genes important for cell cycle progression. p107 and p130 inhibits activity of cyclin/cdk2 complexes. Expression of all those proteins could be regulated by triiodothyronine. In clear cell renal cell carcinoma many disturbances in T3 signaling pathway was described, in that type of cancer also expression of some key G1 to S phase progression regulators was shown.

METHODS

We investigated role of T3 and its receptors in regulation of proliferation of HK2, Caki-2, Caki-1 cell lines (cell counting, cytometric analysis of DNA content) and expression of thyroid hormone receptors, E2F4, E2F5, p107 and p130 (western blot and semi-quantitative real time PCR). Statistical analysis was performed using one-way ANOVA.

RESULTS AND CONCLUSION

We show that T3 inhibits proliferation of HK2, and stimulates it in Caki lines. Those differences are result of disturbed expression of TR causing improper regulation of E2F4, E2F5, p107 and p130 in cancer cells.

摘要

背景

三碘甲状腺原氨酸作为刺激剂或抑制剂调节细胞增殖。与口袋蛋白p107或p130形成复合物的E2F4和E2F5使细胞停滞于G1期，抑制对细胞周期进程重要的基因的转录。p107和p130抑制细胞周期蛋白/细胞周期蛋白依赖性激酶2复合物的活性。所有这些蛋白的表达可能受三碘甲状腺原氨酸调控。在透明细胞肾细胞癌中，已描述了T3信号通路的许多紊乱情况，在这种癌症类型中还显示了一些关键的G1期至S期进展调节因子的表达。

方法

我们研究了T3及其受体在HK2、Caki - 2、Caki - 1细胞系增殖调节中的作用（细胞计数、DNA含量的细胞计量分析）以及甲状腺激素受体、E2F4、E2F5、p107和p130的表达（蛋白质免疫印迹和半定量实时PCR）。使用单向方差分析进行统计分析。

结果与结论

我们发现T3抑制HK2细胞的增殖，并在Caki细胞系中刺激其增殖。这些差异是由于癌细胞中TR表达紊乱导致E2F4、E2F5、p107和p130调节不当的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/491dfe86fdb6/1756-6614-1-5-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/cfcdf899bb76/1756-6614-1-5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/0fdff601d14c/1756-6614-1-5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/69ef7b91231c/1756-6614-1-5-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/85335821de2a/1756-6614-1-5-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/cd6fc9451f11/1756-6614-1-5-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/8dc5a89b553c/1756-6614-1-5-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/491dfe86fdb6/1756-6614-1-5-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/cfcdf899bb76/1756-6614-1-5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/0fdff601d14c/1756-6614-1-5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/69ef7b91231c/1756-6614-1-5-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/85335821de2a/1756-6614-1-5-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/cd6fc9451f11/1756-6614-1-5-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/8dc5a89b553c/1756-6614-1-5-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d0a/2583984/491dfe86fdb6/1756-6614-1-5-7.jpg

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本文引用的文献

1
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Steroids. 2008 Oct;73(9-10):1013-7. doi: 10.1016/j.steroids.2007.12.030. Epub 2008 Jan 16.
2
Thyroid hormone receptor-beta (TR beta 1) impairs cell proliferation by the transcriptional inhibition of cyclins D1, E and A2.甲状腺激素受体β（TRβ1）通过对细胞周期蛋白D1、E和A2的转录抑制来损害细胞增殖。
Oncogene. 2008 Apr 24;27(19):2795-800. doi: 10.1038/sj.onc.1210936. Epub 2007 Nov 26.
3
Overexpression of E2F1 in clear cell renal cell carcinoma: a potential impact of erroneous regulation by thyroid hormone nuclear receptors.
J Signal Transduct. 2016;2016:1362407. doi: 10.1155/2016/1362407. Epub 2016 Mar 13.
4
Identification of common tumor signatures based on gene set enrichment analysis.基于基因集富集分析的常见肿瘤特征识别。
In Silico Biol. 2011;11(1-2):1-10. doi: 10.3233/ISB-2012-0440.
5
Mature mice lacking Rbl2/p130 gene have supernumerary inner ear hair cells and supporting cells.缺乏 Rbl2/p130 基因的成熟老鼠具有多余的内耳毛细胞和支持细胞。
J Neurosci. 2011 Jun 15;31(24):8883-93. doi: 10.1523/JNEUROSCI.5821-10.2011.
6
Iodothyronine deiodinases and cancer.碘甲状腺原氨酸脱碘酶与癌症。
J Endocrinol Invest. 2011 Oct;34(9):716-28. doi: 10.3275/7754. Epub 2011 May 27.
E2F1在透明细胞肾细胞癌中的过表达：甲状腺激素核受体错误调控的潜在影响。
Thyroid. 2007 Nov;17(11):1039-48. doi: 10.1089/thy.2007.0075.
4
Elevated cyclin E level in human clear cell renal cell carcinoma: possible causes and consequences.人透明细胞肾细胞癌中细胞周期蛋白E水平升高：可能的原因及后果
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5
Understanding the natural biology of kidney cancer: implications for targeted cancer therapy.了解肾癌的自然生物学：对靶向癌症治疗的启示。
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6
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Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):193-208. doi: 10.1016/j.beem.2007.04.004.
7
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Acta Biochim Pol. 2006;53(4):641-50. Epub 2006 Nov 19.
8
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Oncogene. 2006 Aug 28;25(38):5201-9. doi: 10.1038/sj.onc.1209652.
9
Current trends in molecular classification of adult renal tumors.成人肾肿瘤分子分类的当前趋势
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10
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Cancer Biol Ther. 2006 Jan;5(1):84-8. doi: 10.4161/cbt.5.1.2345. Epub 2006 Jan 22.