Nanotechnology Now

Our NanoNews Digest Sponsors
Heifer International



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

Virginia Tech physicists propose path to faster, more flexible robots: Virginia Tech physicists revealed a microscopic phenomenon that could greatly improve the performance of soft devices, such as agile flexible robots or microscopic capsules for drug delivery May 17th, 2024

Gene therapy relieves back pain, repairs damaged disc in mice: Study suggests nanocarriers loaded with DNA could replace opioids May 17th, 2024

Shedding light on perovskite hydrides using a new deposition technique: Researchers develop a methodology to grow single-crystal perovskite hydrides, enabling accurate hydride conductivity measurements May 17th, 2024

Oscillating paramagnetic Meissner effect and Berezinskii-Kosterlitz-Thouless transition in cuprate superconductor May 17th, 2024

Nanomedicine

Virginia Tech physicists propose path to faster, more flexible robots: Virginia Tech physicists revealed a microscopic phenomenon that could greatly improve the performance of soft devices, such as agile flexible robots or microscopic capsules for drug delivery May 17th, 2024

Diamond glitter: A play of colors with artificial DNA crystals May 17th, 2024

Advances in priming B cell immunity against HIV pave the way to future HIV vaccines, shows quartet of new studies May 17th, 2024

New micromaterial releases nanoparticles that selectively destroy cancer cells April 5th, 2024

Discoveries

Virginia Tech physicists propose path to faster, more flexible robots: Virginia Tech physicists revealed a microscopic phenomenon that could greatly improve the performance of soft devices, such as agile flexible robots or microscopic capsules for drug delivery May 17th, 2024

Diamond glitter: A play of colors with artificial DNA crystals May 17th, 2024

Finding quantum order in chaos May 17th, 2024

Advances in priming B cell immunity against HIV pave the way to future HIV vaccines, shows quartet of new studies May 17th, 2024

Announcements

Virginia Tech physicists propose path to faster, more flexible robots: Virginia Tech physicists revealed a microscopic phenomenon that could greatly improve the performance of soft devices, such as agile flexible robots or microscopic capsules for drug delivery May 17th, 2024

Diamond glitter: A play of colors with artificial DNA crystals May 17th, 2024

Finding quantum order in chaos May 17th, 2024

Oscillating paramagnetic Meissner effect and Berezinskii-Kosterlitz-Thouless transition in cuprate superconductor May 17th, 2024

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

Aston University researcher receives £1 million grant to revolutionize miniature optical devices May 17th, 2024

Discovery points path to flash-like memory for storing qubits: Rice find could hasten development of nonvolatile quantum memory April 5th, 2024

Chemical reactions can scramble quantum information as well as black holes April 5th, 2024

Discovery of new Li ion conductor unlocks new direction for sustainable batteries: University of Liverpool researchers have discovered a new solid material that rapidly conducts lithium ions February 16th, 2024

Research partnerships

Gene therapy relieves back pain, repairs damaged disc in mice: Study suggests nanocarriers loaded with DNA could replace opioids May 17th, 2024

Discovery points path to flash-like memory for storing qubits: Rice find could hasten development of nonvolatile quantum memory April 5th, 2024

Researchers’ approach may protect quantum computers from attacks March 8th, 2024

How surface roughness influences the adhesion of soft materials: Research team discovers universal mechanism that leads to adhesion hysteresis in soft materials March 8th, 2024

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




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project