跳至主要内容

Tamoxifen Treatment in Correlation with Increased ET-1 Levels Is Associated with the Development of Breast Cancer Metastases

Breast cancer is a hormone-dependent tumor. Apart from chemotherapy, a hormone-therapy is a frequently elected treatment method for patients with positive estrogen receptor status. One important drug for hormone-therapy is Tamoxifen (Tam). Tam binds to both estrogen receptors (alpha and beta) and inhibits the production of specific target genes, important for tumor development.

Endothelin-1 (ET-1), first described as a vasoconstrictor peptide, is also frequently associated with the development of tumors. ET-1 binds via two independent receptors A and B and the expression of these receptors plays an important role in the development of tumors.

The authors in this article analyzed the relationship between Tamoxifen, ET-1 overexpression, and estrogen receptor (ER) leading to Tamoxifen resistance. Breast cancer cell lines were treated with Tamoxifen, ET-1, estrogen and combinations. Using qRT-PCR, immune-precipitation, Western blot, EMSA and immunohistology target gene expression and ER complex partners were investigated. Human biopsies and mastectomy specimens were immunohistologically studied for Vimentin 3, and ERβ. 

The results indicated that breast cancer cells stimulated with a combination of Tamoxifen and ET-1 downregulate ERα, while upregulating intracellular ET-1, and ERβ. Immunoprecipation of nuclear extracts with ET-1, ERα or ERβ agarose conjugated antibodies revealed a complex formation change replacing ERα by ERβ once Tamoxifen formed a complex with ET-1. ERβ and ET-1 migrated into the nucleus. ET-1 stimulation upregulated metastases promoting target genes (IL-6, Wnt11), including a novel one, Vimentin 3. Tissue analyses showed Vim3 and ERβ expression in metastases of ERα positive breast cancer, and in ERα negative biopsies/mastectomy specimens. 

From the observations, it can be concluded that in within the limitations of such a study, ERß seems to be a more important player in ERα positive but also in ERα negative breast cancer, irrespective of the reason for this negativity. The observation of ERß and Vim3 positive tumor parallel the results from the cell culture study, suggesting that the translocation of ET-1 into the nucleus via ERß is responsible for the overproduction of Vim3, which may well be important for cells to lose their anchorage, and leave the cell layer. In short, this concept presents a new treatment approach for individualized medicine in breast cancer patients with increased ET-1 levels.


Article by Melanie von Brandenstein, et al, from Germany and UK.

Full access: http://mrw.so/5pL2sJ

Image by Side Effects1, from Flickr-cc.

评论

发表评论

此博客中的热门博文

Incorporation of High-Altitude Balloon Experiment in High School Science Classrooms

High-altitude balloon is a balloon, filled usually with helium or hydrogen that ascends into an area called “near space” or stratosphere. The most common type of high-altitude balloons are weather balloons. Other purposes include use as a platform for experiments in the upper atmosphere. Modern balloons generally contain electronic equipment such as radio transmitters, cameras, or satellite navigation systems, such as GPS receivers. The mission of the High-Altitude Balloon Experiment (HABE) is to acquire supporting data, validate enabling technologies, and resolve critical acquisition, tracking, and pointing (ATP) and fire control issues in support of future space-based precision pointing experiments. The use of high-altitude balloons offers a relatively low-cost, low-vibration test platform, a recoverable and reusable payload, worldwide launch capability, and a 'near- space' emulation of the future space systems operational scenarios. More recently, several university...
1 条评论
阅读全文

Location Optimization of a Coal Power Plant to Balance Costs against Plant’s Emission Exposure

Fuel and its delivery cost comprise the biggest expense in coal power plant operations. Delivery of electricity from generation to consumers requires investment in power lines and transmission grids. Placing a coal power plant or multiple power plants near dense population centers can lower transmission costs. If a coalmine is nearby, transportation costs can also be reduced. However, emissions from coal plants play a key role in worsening health crises in many countries. And coal upon combustion produces CO 2 , SO 2 , NO x , CO, Metallic and Particle Matter (PM10 & PM2.5). The presence of these chemical compounds in the atmosphere in close vicinity to humans, livestock, and agriculture carries detrimental health consequences. The goal of the research was to develop a methodology to minimize the public’s exposure to harmful emissions from coal power plants while maintaining minimal operational costs related to electric distribution losses and coal logistics. The objective was...
发表评论
阅读全文

Effects of Karate Training on Basic Motor Abilities of Primary School Children

“You never attack first in karate” might be the best conclusion of karate, which is a martial art practiced typically without weapons. It’s reported that karate has a long history for several hundred years, but the modern karate was spread to the whole Japan from Okinawa in the early part of 20th century. Now it has become one of the most widely practiced martial art forms in the world. Usually, it’s divided into Kihon, Kata and Kumite. As for the beginners, Kihon is more suitable for them because it involves basic techniques. Due to karate consists of dynamic offensive and defensive techniques using all parts of the body to their maximum advantage, the best understanding of true karate practice is the perfection of oneself through the perfection of the art. It not only develops coordination, quickens reflexes, and builds stamina, but also develops composure, a clearer thought process, deeper insight into one’s mental capabilities, and more self-confidence. So many researchers stu...
发表评论
阅读全文