• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>British Journal of Cancer >Phorbol ester and bryostatin effects on growth and the expression of oestrogen responsive and TGF-beta 1 genes in breast tumour cells.
【2h】

Phorbol ester and bryostatin effects on growth and the expression of oestrogen responsive and TGF-beta 1 genes in breast tumour cells.

机译：佛波酯和bryostatin对乳腺肿瘤细胞生长以及雌激素反应性和TGF-beta 1基因表达的影响。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) (10 nM) produce a marked reduction in the growth, measured by thymidine uptake, of MCF-7 cells in full growth medium, but had only a small effect on MDA-MB-231 and T47D cells. Bryostatin alone also inhibited growth but to a lesser extent than seen with TPA. The effect of TPA on MCF-7 cells was partially reversed by bryostatin, added simultaneously or after TPA, suggesting bryostatin does not simply mimic TPA in this system. Even though both are believed to act via effects on protein kinase C, bryostatin appears to act as antagonist to the effect of TPA as well as a partial agonist on its own. When the oestrogen receptor positive MCF-7 and T47D cells were maintained in charcoal stripped serum, the increase in DNA synthesis on stimulation with oestradiol was inhibited with 50 nM TPA in MCF-7 cells but not in T47D cells. The effects of these treatments on the expression of two well characterised oestrogen responsive genes pNR2(pS2) and pNR100 (Cathepsin-D) were examined. Rather than preventing transcription of these oestrogen responsive genes, TPA alone increased pNR2 and pNR100 levels in MCF-7 cells and the combined effect of oestradiol and TPA had a marked synergistic effect in increasing the transcript levels of these genes. In T47D cells pNR2 transcripts were not detected and the increase in pNR100 mRNA levels were not affected by TPA. We conclude that the inhibitory effects of TPA on the growth stimulation of MCF-7 cells by oestradiol was not due to a general inhibition of the expression of oestrogen responsive genes. An alternative possibility examined was that the growth inhibitory effect of TPA on MCF-7 cells might be due to stimulation of TGF-beta 1, acting as an autocrine inhibitory growth factor. Oestradiol treatment of MCF-7 cells reduced the levels of TGF-beta 1 mRNA whereas TPA produced a marked increase. The combined effect of TPA and oestradiol further increased TGF-beta 1 mRNA above the levels seen with TPA alone. Bryostatin had little effect on TGF-beta 1 expression either alone or in combination with oestradiol. These observations are consistent with the hypothesis that the inhibitory effect of TPA on MCF-7 cells may be partly due to autocrine inhibition by TGF-beta 1.
机译：佛波醇酯12-O-十四烷酰佛波醇13-乙酸酯（TPA）（10 nM）在完全生长的培养基中可显着降低MCF-7细胞的生长（通过胸腺嘧啶核苷的摄取），但对MDA-MB-231和T47D细胞。单独的生长抑素也抑制生长，但程度比TPA少。 TPA对MCF-7细胞的作用被抑菌素部分逆转，可以同时或在TPA之后加入，这表明抑菌素不能简单地在该系统中模拟TPA。尽管据信两者都通过作用于蛋白激酶C而起作用，但抑菌素似乎可以作为TPA的拮抗剂并单独发挥部分激动剂的作用。当在木炭剥离的血清中维持雌激素受体阳性的MCF-7和T47D细胞时，用雌二醇刺激的DNA合成的增加在MCF-7细胞中被50 nM TPA抑制，而在T47D细胞中不被抑制。检查了这些处理对两个特征明确的雌激素响应基因pNR2（pS2）和pNR100（组织蛋白酶-D）表达的影响。并不是阻止这些雌激素应答基因的转录，而是单独使用TPA会增加MCF-7细胞中的pNR2和pNR100水平，而雌二醇和TPA的联合作用在增加这些基因的转录水平方面具有明显的协同作用。在T47D细胞中，未检测到pNR2转录本，而pNR100 mRNA水平的升高不受TPA的影响。我们得出结论，TPA对雌二醇对MCF-7细胞生长刺激的抑制作用不是由于普遍抑制雌激素反应基因的表达。检查的另一种可能性是，TPA对MCF-7细胞的生长抑制作用可能是由于TGF-β1的刺激，该TGF-β1作为自分泌抑制性生长因子。雌二醇对MCF-7细胞的处理降低了TGF-β1mRNA的水平，而TPA产生了明显的增加。 TPA和雌二醇的联合作用进一步提高了TGF-β1mRNA的水平，超过了单独使用TPA所见的水平。单独或与雌​​二醇联合使用，Bryostatin对TGF-β1表达几乎没有影响。这些观察结果与TPA对MCF-7细胞的抑制作用可能部分归因于TGF-beta 1对自分泌的抑制作用有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号