Researchers find protein that mediates formation of HER2-driven breast cancer

January 9, 2018 by Katie Pence, University of Cincinnati Academic Health Center
Credit: CC0 Public Domain

Researchers at the University of Cincinnati College of Medicine have identified for the first time that the estrogen receptor-binding protein MED1 is a critical mediator of HER2-driven breast cancer, identifying it as a potential therapeutic target.

MED1 is a protein often produced, or expressed, at abnormally high levels in cells that when eliminated is found to stop cancer cell growth; HER2 breast cancer involves a protein called human epidermal growth factor receptor 2, which promotes the growth of cancer cells.

These findings, published ahead of print in the Jan. 8 online edition of the journal Cancer Research, could lead to better, more effective treatments for aggressive and treatment-resistant breast cancer.

"Breast cancer remains one of the most common cancers and is one of the leading causes of death for women in the U.S.," says Xiaoting Zhang, PhD, associate professor in the Department of Cancer Biology at the UC College of Medicine, member of the Cincinnati Cancer Center and the UC Cancer Institute and lead author on this study. "Studies have divided breast cancer into several subtypes based on gene expression of , progesterone receptor and/or HER2. MED1 is an receptor coactivator that has been shown to play important roles in estrogen receptor-dependent functions in both mammary gland development and breast cancer.

"Interestingly, the MED1 gene is located very close to and amplified together with HER2 in the gene, and the MED1 protein levels are highly linked to HER2-positive breast cancer. Additionally, we've found that HER2 can activate MED1, and MED1 functions as a key 'crosstalk' point between the HER2 and estrogen receptor pathway in the treatment resistance of HER2 and estrogen receptor double positive breast cancer. However, the role and underlying molecular functions of MED1 in HER2-driven breast cancer development and spread is still poorly understood."

Zhang says in this study, researchers generated animal models with the HER2 cancer gene and the mutation of MED1 to evaluate the protein's role in breast cancer progression and spread.

"The estrogen receptor specifically binds the MED1 protein in the regions known as the LxxLL motifs. We found that mutating MED1 in the LxxLL motifs disrupted its interaction with the estrogen receptor and significantly delayed tumor growth, spread and cancer stem-like cell formation in this model," Zhang says. "This is the first evidence indicating that MED1 and its LxxLL motifs play a critical role in breast cancer formation, metastasis and cancer stem cell formation. This is also the first time a gene co-amplified with HER2 has been shown to play a role in HER2-driven cancer formation. Further investigations looking at the mechanisms underlying MED1 functions revealed that it acted directly to regulate estrogen signaling through the downstream IGF-1 pathway, a key pathway known to play critical roles in breast cancer. Importantly, human patient samples showed a strong correlation between MED1 and IGF-1 protein levels, further supporting the potential of MED1 and its LxxLL motifs as therapeutic targets.

"With these findings and our previously published study showing a tissue-specific role for MED1, we can now conduct further studies on MED1 as a disease-selective therapeutic target. Our team is currently using an RNA nanotechnology-based approach to select RNA aptamers (RNA molecules that bind to a specific target molecule) to specifically target MED1 LxxLL motifs to disrupt the MED1/estrogen receptor interactions to achieve this."

Explore further: New finding gives clues for overcoming tamoxifen-resistant breast cancer

Related Stories

New finding gives clues for overcoming tamoxifen-resistant breast cancer

November 2, 2012
(Medical Xpress)—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 ...

Researchers identify potential therapeutic target in aggressive breast cancer cells

November 15, 2017
An especially aggressive breast cancer cell can respond to hormone therapy if they express a specific protein known as estrogen receptor beta (ERβ), according to new research published on the cover of Oncotarget. The findings ...

Novel therapeutic target discovered for estrogen receptor positive (ER+) breast cancer

November 17, 2017
Researchers at the Icahn School of Medicine at Mount Sinai have identified a protein that can be targeted to suppress growth of a common type of breast cancer known as "estrogen receptor positive" (ER+), including ER+ cancers ...

Team finds potential clue associated with aggressive prostate cancer

August 20, 2013
Prostate cancer is one of the most common forms of cancer in men and the leading cause of cancer deaths in white, African-American and Hispanic men, according to the Centers for Disease Control. Current treatment of prostate ...

Breast cancer recurrence defined by hormone receptor status

October 1, 2012
Human epidermal growth factor (HER2) positive breast cancers are often treated with the same therapy regardless of hormone receptor status. New research published in BioMed Central's open access journal Breast Cancer Research ...

Recommended for you

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.