Nanotechnology Now

Our NanoNews Digest Sponsors


Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > New Clues For Overcoming Tamoxifen-Resistant Breast Cancer

Zhang's research model showing HER2 activation of MED1 drives estrogen receptor corepressor/coactivator switch by tamoxifen.Credit University of Cincinnati
Zhang's research model showing HER2 activation of MED1 drives estrogen receptor corepressor/coactivator switch by tamoxifen.

Credit University of Cincinnati

Abstract:
A University of Cincinnati (UC) cancer biology team reports breakthrough findings about specific cellular mechanisms that may help overcome endocrine (hormone) therapy-resistance in patients with estrogen-positive breast cancers, combating a widespread problem in effective medical management of the disease.

New Clues For Overcoming Tamoxifen-Resistant Breast Cancer

Cincinnati, OH | Posted on November 5th, 2012

Xiaoting Zhang, PhD, and his colleagues have identified a specific estrogen receptor co-activator—known as MED1—as playing a central role in mediating tamoxifen resistance in human breast cancer. The team reports its findings in the Nov. 1, 2012, issue of Cancer Research, a scientific journal of the American Association for Cancer Research.

According to the National Cancer Institute, nearly 227,000 women are diagnosed with breast cancer annually in the United States. About 75 percent have estrogen-positive tumors and require adjuvant hormone therapy such as tamoxifen, a drug that works by interfering with estrogen's ability to stimulate breast cancer cell growth.

Despite advances in hormone therapy drugs, cancer surveillance research has shown that 50 percent of patients will develop resistance to the drug and experience a cancer relapse.

The hormones estrogen and progesterone can stimulate the growth of some breast cancers. Hormone therapy is used to stop or slow the growth of these tumors. Hormone-sensitive (i.e., positive) breast cancer cells contain specific proteins known as hormone receptors that become activated once hormones bind to them, leading to cancer growth.

Based on new findings, UC Cancer Institute scientists believe that tamoxifen resistance may be driven by a novel molecular "crosstalk" point between the estrogen and HER2 (human epidermal growth factor receptor 2) signaling pathways.

Testing in both pre-clinical models and human breast cancer tissue samples showed that MED1 co-amplifies and co-expresses with HER2, a gene that has an increased presence in 20-30 percent of invasive human breast cancer and plays a major role in tamoxifen resistance.

HER2 over-expression led to MED1 activation while reduction of MED1 caused breast cancer cells that were otherwise tamoxifen-resistant to respond and stop dividing. Further mechanistic studies showed that HER2 activation of MED1 resulted in the recruitment of co-activators instead of co-repressors by tamoxifen-bound estrogen receptor. This, explains Zhang, drives expression of not only traditional estrogen receptor-positive cancer target genes, but also HER2 and those estrogen receptor target genes abnormally activated by HER2.

"Together, these findings suggest this ‘crosstalk' could play a central role in mediating tamoxifen resistance in human breast cancer, especially because recent published data also indicated that high MED1 expression levels correlate with poor treatment outcome and disease-free survival of patients who underwent endocrine therapy," explains Zhang, an assistant professor of cancer biology at the UC College of Medicine and breast cancer researcher with the UC Cancer Institute.

"We are currently utilizing RNA-based nanotechnology to target MED1 in an effort to simultaneously block both estrogen and HER2 pathways to overcome endocrine-resistant breast cancer."

UC study collaborators include cancer biologists Jiajun Cui, PhD, Katherine Germer, MD, Shao-chun Wang, PhD; environmental health researcher Tianying Wu, PhD; and pathologist Jiang Wang, MD. Qianben Wang, PhD of the Ohio State University College of Medicine, and Jia Luo, PhD, of the University of Kentucky, also contributed to this study.

The study was supported with start-up funding from the UC Cancer Institute, Ride Cincinnati/Marlene Harris Pilot Grant, Susan G. Komen for the Cure Foundation and the Center for Clinical and Translational Science and Training—home to UC's institutional Clinical and Translational Science Award program grant from the National Institutes of Health.

####

About University of Cincinnati
The University of Cincinnati Cancer Institute is one of four UC and UC Health collaborative centers of excellence for research, patient care and education. The UC Cancer Institute and Cincinnati Children’s Hospital Medical Center Cancer and Blood Diseases Institute together form the Cincinnati Cancer Center, a joint cancer initiative aimed at advancing cancer care faster through innovative research.

For more information, please click here

Contacts:
Amanda Harper
513-558-4657

Copyright © University of Cincinnati

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related Links

Cross-talk between HER2 and MED1 Regulates Tamoxifen Resistance of Human Breast Cancer Cells. Cancer Res, November 1, 2012 72:5625-5634; Published OnlineFirst September 10, 2012; doi: 10.1158/0008-5472.CAN-12-1305

Related News Press

News and information

JPK reports on the use of a NanoWizard AFM system at the University of Kaiserslautern to study the interaction of bacteria with microstructured surfaces April 28th, 2016

University of Illinois researchers create 1-step graphene patterning method April 27th, 2016

Nanograft seeded with 3 cell types promotes blood vessel formation to speed wound healing April 27th, 2016

NREL finds nanotube semiconductors well-suited for PV systems April 27th, 2016

Nanomedicine

JPK reports on the use of a NanoWizard AFM system at the University of Kaiserslautern to study the interaction of bacteria with microstructured surfaces April 28th, 2016

Danish researchers behind vaccine breakthrough April 27th, 2016

Researchers create artificial protein to control assembly of buckyballs April 27th, 2016

Chemists use DNA to build the world's tiniest thermometer April 27th, 2016

Discoveries

Nanograft seeded with 3 cell types promotes blood vessel formation to speed wound healing April 27th, 2016

NREL finds nanotube semiconductors well-suited for PV systems April 27th, 2016

Danish researchers behind vaccine breakthrough April 27th, 2016

NREL theory establishes a path to high-performance 2-D semiconductor devices April 27th, 2016

Announcements

JPK reports on the use of a NanoWizard AFM system at the University of Kaiserslautern to study the interaction of bacteria with microstructured surfaces April 28th, 2016

University of Illinois researchers create 1-step graphene patterning method April 27th, 2016

Researchers create artificial protein to control assembly of buckyballs April 27th, 2016

Chemists use DNA to build the world's tiniest thermometer April 27th, 2016

Grants/Awards/Scholarships/Gifts/Contests/Honors/Records

Brookhaven's Oleg Gang Named a Battelle 'Inventor of the Year': Recognized for work using DNA to guide and regulate the self-assembly of nanoparticles into clusters and arrays with controllable properties April 25th, 2016

Zip software can detect the quantum-classical boundary: Compression of experimental data reveals the presence of quantum correlations April 21st, 2016

Making electronics out of coal: Instead of burning up this complex hydrocarbon, let's make devices from it April 20th, 2016

Nano-magnets produce 3-dimensional images: Wide-view 3-dimensional holographic display composed of nano-magnetic pixels April 20th, 2016

Research partnerships

Nanograft seeded with 3 cell types promotes blood vessel formation to speed wound healing April 27th, 2016

NREL finds nanotube semiconductors well-suited for PV systems April 27th, 2016

Flipping a chemical switch helps perovskite solar cells beat the heat April 26th, 2016

XEI Scientific and the University of Southern California collaborate on the use of downstream plasma cleaning in sample preparation and publish a paper in ACS Photonics April 26th, 2016

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







Car Brands
Buy website traffic