Scientists find cell pathway driving a deadly sub-type of breast cancer

November 15, 2008

An intra cellular pathway not previously linked to breast cancer is driving a sub-type of the disease that is highly lethal and disproportionately over-represented in African American women.

The pathway regulates how cells identify and destroy proteins and represents a class of genes called proteasome targeting complexes. The work shows that basal cancer cells degrade the tumor suppressor gene p27 by making a new type of proteasome targeting complex. The gene p27 is one of a handful of proteins that are expressed in normal cells and act to prevent rapid cell growth, which is indicative of cancer. Beyond chemotherapy, no specific therapeutic target has been identified for this sub-type of cancer, found in between 12 to 15 percent of breast cancers in the general population and up to 25 percent of cases in African American women.

"The mortality rates in this subgroup of cancer are very high," said Tim Lane, senior author of the paper and a researcher at UCLA's Jonsson Comprehensive Cancer Center. "The possibility that this new proteasome targeting complex might provide targets for therapeutic intervention is a completely new area for breast cancer research."

The research, done in animal models and human breast cancer cell lines, is published in the Nov. 15 issue of the journal Genes and Development.

Scientists have identified five to seven different sub-types of breast cancer. Basal-like breast cancers currently are among the most difficult to treat.

Targeted therapeutics are available for several sub-types. Women with HER-2 positive breast cancers can receive Herceptin, which when paired with chemotherapy extends disease-free survival by more than 50 percent. HER-2 positive women used to have the worst prognoses before Herceptin was developed. They now have the best prognoses because the drug targets what's broken in the cancer cell that is driving the disease. Another sub-type includes women with Estrogen Receptor positive cancers. These patients have several drugs available, such as Tamoxifen, that suppress the actions of estrogen on breast cancer tissue and thus control the disease.

Next up, Lane and his team plan to use protein chemistry and genetic tools to uncover the molecular components that participate in this new proteasome targeting complex, which could identify alterations – like HER-2 - that can be targeted in cancer cells and leave the healthy cells alone. That would give patients with this aggressive cancer sub-type a more effective and less toxic option than chemotherapy.

"This research has the potential to identify clinically relevant markers of a large subgroup of human breast cancer and find a novel therapeutic target that could be exploited with appropriate pharmaceutical agents," said Lane, who is an associate professor of obstetrics and gynecology. "We need a new paradigm to think about how to treat these cancers."

Lane's research also showed that basal-like breast cancer cells are most like breast stem cells, which generate the tissues of the breast. One way they're alike is that they are resistant to chemotherapy and do not express mature breast markers like estrogen receptor. These features make basal-like breast cancers so difficult to treat.

Another mystery Lane and his team hope to focus on is why basal-like breast cancers are over-represented in African American women. It could be related to genetic features in the patient, or to other complex factors such as access to effective early intervention, Lane said.

Lane is currently working to validate his work in human disease and identify all the key players in this molecular pathway.

"We're still missing a couple of the key players. We currently understand the shape and general features of the complex, but hope to find all the components in the next couple of years," Lane said. "It is a great time to be involved in this research."

Source: University of California - Los Angeles

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

Related Stories

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.

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

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 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 ...

How pomegranate extract alters breast cancer stem cell properties

November 15, 2017
A University at Albany research team has found evidence suggesting that the same antioxidant that gives pomegranate fruit their vibrant red color can alter the characteristics of breast cancer stem cells, showing the superfood's ...

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 ...

Recommended for you

Clinical trial suggests new cell therapy for relapsed leukemia patients

November 20, 2017
A significant proportion of children and young adults with treatment-resistant B-cell leukemia who participated in a small study achieved remission with the help of a new form of gene therapy, according to researchers at ...

Study reveals new mechanism used by cancer cells to disarm attacking immune cells

November 20, 2017
A new study by researchers at The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute (OSUCCC - James) identifies a substance released by pancreatic cancer cells that protects ...

Cell-weighing method could help doctors choose cancer drugs

November 20, 2017
Doctors have many drugs available to treat multiple myeloma, a type of blood cancer. However, there is no way to predict, by genetic markers or other means, how a patient will respond to a particular drug. This can lead to ...

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

E_L_Earnhardt
not rated yet Nov 16, 2008
Where the tumor is enclosed cool sterille water drip should reduce mitosing cells. (cyroablation)
Drain is vital!

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.