Study examines the mechanisms that silence the estrogen receptor gene alpha during breast cancer

August 17, 2007

The mechanisms that silence the estrogen receptor gene alpha (ER-á) in certain breast cancer cell lines may be closer to being unlocked, according to a study by researchers at Temple University’s Sbarro Institute for Cancer Research and Molecular Medicine.

The researchers reported their findings, “Epigenetic Modulation of Estrogen Receptor-á by pRb Family Proteins: A Novel Mechanism in Breast Cancer,” in the Aug. 15 issue of the journal Cancer Research.

In a previous study, the researchers found that in estrogen receptor-positive and estrogen receptor-negative mammary cell lines of women who have been affected with breast cancer, the tumor-suppressing gene pRb2/p130 binds to a specific region of the estrogen receptor gene alpha and forms molecular complexes recruiting and/or interacting with several proteins. They discovered that in estrogen receptor-negative cells — which are able to silence the expression of the estrogen receptor — pRb2/p130 forms a specific molecular complex recruiting a different sequence of proteins than in the estrogen receptor–positive cells.

In the current study, lead by Antonio Giordano, M.D., Ph.D., director of the Sbarro Institute (www.shro.org), the researchers showed that the presence of specific pRb2/p130 multimolecular complexes bound to the estrogen receptor gene strongly correlates with the methylation (chemical modification) of the gene. “Our hypothesis is that the sequence of epigenetic events for establishing and maintaining the silenced state of the estrogen receptor gene alpha during the breast cancer progression is mediated by pRb2/p130 in association with specific proteins that modified the DNA structure through specific mechanisms,” said Giordano, who discovered the Rb2 gene while working at Temple’s Fels Cancer Institute in the early 1990s.

“In other words, the presence of a specific pRb2/p130 multimolecular complex may dictate a local change of the DNA structure of the estrogen receptor alpha gene and influence its susceptibility to chemical modification (DNA methylation), as well as to different epigenetic alterations leading to estrogen receptor alpha silencing,” added Marcella Macaluso, research assistant professor at the Sbarro Institute and the study’s lead author.

Giordano says this study provides a basis for understanding how the complex pattern of estrogen receptor gene alpha methylation and transcriptional silencing is generated, as well as for understanding the relationship between this pattern and its function during breast cancer progression. By understanding this mechanism of how pRb2/p130 recruits molecules, he says, researchers will be able to design therapies and drugs that are very precise in the target they recognize. “One gene on its own doesn’t mean anything,” he explains. “It’s the dialogue among the genes that are writing the sentences, and this finding really writes a very important sentence in the book that we are authoring on uncovering the understanding of how a normal cell functions and why some therapies work or some therapies don’t work. It also clearly shows that cancer is not the event of one gene, but an army of genes and it looks like pRb2/p130 is one of the generals.”

Source: Temple University

Explore further: Researchers find new biomarker for breast cancer

Related Stories

Researchers find new biomarker for breast cancer

November 20, 2017
With the support of the FWF, an oncologist found a biomarker for breast cancer having a poor prognosis and developed two viable methods to detect it in tissue samples.

Researchers discover a new target for 'triple-negative' breast cancer

November 20, 2017
So-called "triple-negative" breast cancer is a particularly aggressive and difficult-to-treat form. It accounts for only about 10 percent of breast cancer cases, but is responsible for about 25 percent of breast cancer fatalities.

Team explores anti-breast cancer properties of soy

October 30, 2017
A University of Arizona Cancer Center research team is engaged in a series of studies to investigate how genistein, a component of soy foods, might suppress the development of breast cancer.

Prenatal exposure to BPA at low levels can affect gene expression in developing rat brain

October 31, 2017
New research from North Carolina State University reveals that prenatal exposure to bisphenol A (BPA) at levels below those currently considered safe for humans affects gene expression related to sexual differentiation and ...

Sight unseen: Gene Expression reveals 'hidden' variability in cancer cells' response to drugs

October 30, 2017
A study led by scientists from Harvard Medical School reveals "hidden" variability in how tumor cells are affected by anticancer drugs, offering new insights on why patients with the same form of cancer can have different ...

Researchers use gene therapy to extend estrogen's protective effects on memory

December 8, 2015
The hormone estrogen helps protect memory and promote a healthy brain, but this effect wanes as women age, and even estrogen replacement therapy stops working in humans after age 65. Now researchers at University of Florida ...

Recommended for you

Researchers unravel novel mechanism by which tumors grow resistant to radiotherapy

November 23, 2017
A Ludwig Cancer Research study has uncovered a key mechanism by which tumors develop resistance to radiation therapy and shown how such resistance might be overcome with drugs that are currently under development. The discovery ...

African Americans face highest risk for multiple myeloma yet underrepresented in research

November 23, 2017
Though African-American men are three times more likely to be diagnosed with multiple myeloma, a type of blood cancer, most scientific research on the disease has been based on people of European descent, according to a study ...

Encouraging oxygen's assault on iron may offer new way to kill lung cancer cells

November 22, 2017
Blocking the action of a key protein frees oxygen to damage iron-dependent proteins in lung and breast cancer cells, slowing their growth and making them easier to kill. This is the implication of a study led by researchers ...

One-size treatment for blood cancer probably doesn't fit all, researchers say

November 22, 2017
Though African-American men are three times more likely to be diagnosed with a blood cancer called multiple myeloma, most scientific research on the disease has been based on people of European descent, according to a study ...

One in four U.S. seniors with cancer has had it before

November 22, 2017
(HealthDay)—For a quarter of American seniors, a cancer diagnosis signals the return of an old foe, new research shows.

Combination immunotherapy targets cancer resistance

November 22, 2017
Cancer immunotherapy drugs have had notable but limited success because in many cases, tumors develop resistance to treatment. But researchers at Yale and Stanford have identified an experimental antibody that overcomes this ...

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.