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雌激素通过诱导细胞凋亡、降低c-myb蛋白水平以及减少抗凋亡蛋白bcl-2的转录来阻止COLO-205人结肠癌细胞的持续生长。

Estrogen prevents sustained COLO-205 human colon cancer cell growth by inducing apoptosis, decreasing c-myb protein, and decreasing transcription of the anti-apoptotic protein bcl-2.

作者信息

Wilkins Heather R, Doucet Kristin, Duke Victoria, Morra Amber, Johnson Nicole

机构信息

Department of Natural Sciences, Assumption College, 500 Salisbury Street, Worcester, MA 01609, USA.

出版信息

Tumour Biol. 2010 Jan;31(1):16-22. doi: 10.1007/s13277-009-0003-2. Epub 2009 Dec 18.

Abstract

The proto-oncogene c-myb is overexpressed in human colon cancer cells. c-myb is known to be affected by estrogen in some breast cancers and leukemias. However, the mechanism of c-myb regulation via estrogen in colon cancer requires further investigation. Human COLO-205 colon cancer cells were cultured and treated with beta-estradiol for 24 h. Apoptosis was quantified using acridine orange/propidium iodide labeling and confirmed with DNA fragmentation gel electrophoresis. Expression of c-myb protein was assessed via SDS-PAGE and immunoblotting and RT-PCR was used to quantify bcl-2 RNA. Protein and RNA expression levels were also assayed after c-myb siRNA treatment for 24 h. We demonstrate an increase in apoptosis after 24 h of beta-estradiol treatment of human COLO-205 colon cancer cells. Estrogen treatment also decreases c-myb protein levels as well as expression of its transcriptional target bcl-2. Suppression of c-myb protein also results in increased apoptosis and decreases bcl-2 expression. These results indicate that estrogen has a protective effect from sustained colon cancer cell growth at least partly through suppression of c-myb and bcl-2.

摘要

原癌基因c-myb在人结肠癌细胞中过表达。已知c-myb在某些乳腺癌和白血病中受雌激素影响。然而,在结肠癌中通过雌激素调节c-myb的机制需要进一步研究。培养人COLO-205结肠癌细胞并用β-雌二醇处理24小时。使用吖啶橙/碘化丙啶标记定量凋亡,并用DNA片段凝胶电泳进行确认。通过SDS-PAGE和免疫印迹评估c-myb蛋白的表达,并用RT-PCR定量bcl-2 RNA。在c-myb siRNA处理24小时后也检测蛋白质和RNA表达水平。我们证明,人COLO-205结肠癌细胞经β-雌二醇处理24小时后凋亡增加。雌激素处理还降低了c-myb蛋白水平及其转录靶标bcl-2的表达。c-myb蛋白的抑制也导致凋亡增加并降低bcl-2表达。这些结果表明,雌激素至少部分地通过抑制c-myb和bcl-2对持续的结肠癌细胞生长具有保护作用。

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