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血管紧张素 1-9 和血管紧张素 3-7 在前列腺上皮细胞中的相反作用。

The opposite effects of angiotensin 1-9 and angiotensin 3-7 in prostate epithelial cells.

机构信息

Department of Comparative Endocrinology, Medical University of Lodz, Lodz, 90-752, Poland.

Department of Laboratory of Cell Cultures and Genomic Analysis, Medical University of Lodz, Lodz, 90-752, Poland.

出版信息

Biochem Biophys Res Commun. 2019 Nov 19;519(4):868-873. doi: 10.1016/j.bbrc.2019.09.079. Epub 2019 Sep 25.

Abstract

There is growing evidence that renin-angiotensin system (RAS) components have been involved in the development of various types of cancers, including prostate cancer. This article for the first time reports the impact of Ang1-9 and Ang3-7 on viability and proliferation, migration and invasion of epithelial prostate cells. The results of this study clearly show that Ang1-9 and Ang3-7 exert different/opposite effects on in vitro biological properties of prostate cells. It appears that Ang1-9 has pro-cancer activities via the ability to induce cell divisions, enhance cell motility and stimulate the expression of such genes as vascular endothelial growth factor (VEGF), hypoxia-inducible factors (HIF-1), vimentin (VIM) and REL proto-oncogene, NF-kB subunit (REL). On the contrary, Ang3-7 did not show any mitogenic activity. Furthermore, this peptide hormone limited the migration of PNT1A cells probably by downregulation of VEGF and VIM expression. Finally, it is worth noting that both angiotensins have the ability to modulate gene expression for angiotensin receptors. Unfortunately, we could not unequivocally identify the type of angiotensin receptor responsible for signal transduction pathway involved in PNT1A cell survival and proliferation. Undoubtedly, further research and testing in this area are necessary.

摘要

越来越多的证据表明,肾素-血管紧张素系统(RAS)成分参与了各种类型癌症的发展,包括前列腺癌。本文首次报道了血管紧张素 1-9(Ang1-9)和血管紧张素 3-7(Ang3-7)对前列腺上皮细胞活力和增殖、迁移和侵袭的影响。本研究结果清楚地表明,Ang1-9 和 Ang3-7 对前列腺细胞的体外生物学特性有不同/相反的作用。Ang1-9 似乎通过诱导细胞分裂、增强细胞迁移和刺激血管内皮生长因子(VEGF)、缺氧诱导因子(HIF-1)、波形蛋白(VIM)和 REL 原癌基因、NF-kB 亚基(REL)等基因的表达,发挥促癌作用。相反,Ang3-7 没有表现出任何有丝分裂活性。此外,这种肽激素可能通过下调 VEGF 和 VIM 的表达来限制 PNT1A 细胞的迁移。最后,值得注意的是,这两种血管紧张素都有能力调节血管紧张素受体的基因表达。不幸的是,我们不能明确确定负责参与 PNT1A 细胞存活和增殖的信号转导途径的血管紧张素受体的类型。毫无疑问,在这一领域进一步的研究和测试是必要的。

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