Angiotensin II stimulation of Na+/K+ATPase activity and cell growth by calcium-independent pathway in MCF-7 breast cancer cells
Angiotensin II stimulation of Na+/K+ATPase activity and cell growth by calcium-independent pathway in MCF-7 breast cancer cells
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DOI：
10.1677/joe.0.1730315
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发表时间：
2002-05-01
影响因子：
4
通讯作者：
Marsigliante, S
中科院分区：
文献类型：
--
作者：
Muscella, A;Greco, S;Marsigliante, S
在这里，我们通过RT-PCR分析证明，血管紧张素II(Ang II)受体亚型AT1和AT2在乳腺癌上皮细胞系中都有表达。McF-7。Ang II不能影响Fura-2负载细胞内的钙离子浓度，提示AT1介导的磷脂水解不参与其细胞内信号转导途径。Ang II以剂量和时间依赖的方式调节Na+/K(+)ATPase的活性，并且是有丝分裂的，具有剂量依赖性(1-1000 nM)的增殖效应，在100 nM时反应最大。AT1受体拮抗剂DUP 753可完全阻断Ang II与AT1的结合，介导Na+/K(+)ATPase的激活和增殖。血管紧张素Ⅱ受体拮抗剂CGp 42112不影响血管紧张素Ⅱ的活性。本研究的主要结论是，血管紧张素Ⅱ通过激活血管紧张素转换酶1来影响乳腺癌细胞MCF7的细胞增殖和Na+/K(+)ATPase，而不依赖于钙信号转导机制。
Here we demonstrated by PT-PCR analysis, the expression of both angiotensin II (Ang II) receptor subtypes, AT1 and AT2, in a breast cancer epithelial cell line. MCF-7. Ang II was not able to affect the intracellular Ca2+ concentration in Fura-2 loaded cells suggesting that AT1-mediated phospholipid hydrolysis is not involved in its intracellular transduction pathway. Ang II modulated the activity of the Na+/K(+)ATPase in a dose- and time-dependent manner and was mitogenic, with a dose-dependent (1-1000 nM) proliferative effect and a maximal response at 100 nM. Both Na+/K(+)ATPase activation and stimulation of proliferation were mediated by binding of Ang II to AT1, as the effects were completely blocked by Dup 753, a specific AT1 antagonist. CGP 42112, an AT2 antagonist, did not affect Ang II actions.The main conclusion of this study is that Ang II exerts its effects on cell proliferation and Na+/K(+)ATPase in breast cancer epithelial cells, MCF-7, via AT1 activation independently of the Ca2+ signalling mechanism.