Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma.
Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma.
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DOI：
10.1038/sj.bjc.6601646
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发表时间：
2004-03-08
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
在人胶质母细胞瘤中评估了肾素-血管紧张素系统（RAS）在生长和凋亡中的表达和功能。通过原位杂交和免疫组织化学在胶质母细胞瘤细胞中发现了肾素和血管紧张素原 (AGT) mRNA 和蛋白质。血管紧张素原存在于胶质母细胞瘤囊液中。因此，人胶质母细胞瘤细胞产生肾素和AGT并分泌AGT。人胶质母细胞瘤和胶质母细胞瘤细胞分别表达肾素、AGT、肾素受体、AT2 和/或 AT1 mRNA 以及通过 RT-PCR 和/或蛋白质印迹法测定的蛋白质。使用培养的人胶质母细胞瘤细胞研究了 RAS 在胶质母细胞瘤中的功能。将血管紧张素原、des(Ang I)AGT、十四肽肾素底物 (AGT1-14)、Ang I、Ang II 或 Ang III 添加到培养的胶质母细胞瘤细胞中，不会调节其增殖、存活或死亡。血管紧张素转换酶抑制剂不会减少胶质母细胞瘤细胞的增殖。然而，向胶质母细胞瘤细胞中添加选择性合成肾素抑制剂会降低 DNA 合成和活肿瘤细胞数量，并诱导细胞凋亡。同时添加 Ang II 并不能抵消这种作用。总之，完整的 RAS 由人胶质母细胞瘤和培养的胶质母细胞瘤细胞表达。抑制胶质母细胞瘤细胞中的肾素可能是控制胶质母细胞瘤细胞增殖和存活以及联合治疗中胶质母细胞瘤进展的潜在方法。
The expression and function in growth and apoptosis of the renin–angiotensin system (RAS) was evaluated in human glioblastoma. Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells. Angiotensinogen was present in glioblastoma cystic fluids. Thus, human glioblastoma cells produce renin and AGT and secrete AGT. Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT2 and/or AT1 mRNAs and proteins determined by RT–PCR and/or Western blotting, respectively. The function of the RAS in glioblastoma was studied using human glioblastoma cells in culture. Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1–14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death. Angiotensin-converting enzyme inhibitors did not diminish glioblastoma cell proliferation. However, the addition of selective synthetic renin inhibitors to glioblastoma cells decreased DNA synthesis and viable tumour cell number, and induced apoptosis. This effect was not counterbalanced by concomitant addition of Ang II. In conclusion, the complete RAS is expressed by human glioblastomas and glioblastoma cells in culture. Inhibition of renin in glioblastoma cells may be a potential approach to control glioblastoma cell proliferation and survival, and glioblastoma progression in combination therapy.
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DOI：
10.1073/pnas.90.14.6796
发表时间：
1993-07-15
影响因子：
11.1
作者：
BALDWIN, ET;BHAT, TN;ERICKSON, JW
通讯作者：
ERICKSON, JW
影响因子：
19.6
作者：
Nguyen, G;Delarue, F;Sraer, JD
通讯作者：
Sraer, JD
影响因子：
4.8
作者：
Célérier, J;Schmid, G;Jeunemaitre, X
通讯作者：
Jeunemaitre, X
影响因子：
15.9
作者：
GALEN, FX;DEVAUX, C;PAU, B
通讯作者：
PAU, B
影响因子：
5.8
作者：
JUILLERATJEANNERET, L
通讯作者：
JUILLERATJEANNERET, L