Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein Linked to Therapy Resistance in Breast Cancer

12.09.2012
Berkeley Lab Researchers Identify Possible New Oncogene and Future Therapy Target
A gene that may possibly belong to an entire new family of oncogenes has been linked by researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) with breast cancer resistance to a well-regarded and widely used cancer therapy.

One of the world’s leading breast cancer researchers, Mina Bissell, Distinguished Scientist with Berkeley Lab’s Life Sciences Division, led a study in which a protein known as FAM83A was linked to resistance to the cancer drugs known as EGFR-TKIs (Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors). Not only may this discovery explain the clinical correlation between a high expression of FAM83A and a poor prognosis for breast cancer patients, it may also provide a new target for future therapies.

“Resistance to EGFR-TKIs has limited their use for breast cancer treatment and until now the mechanisms behind this resistance have largely been a mystery,” Bissell says. “We’ve demonstrated, both in cultured cells and in mice, that FAM83A has oncogenic properties and when overexpressed in cancer cells confers EGFR-TKI resistance and promotes the proliferation and invasion of tumors.”

Bissell is the corresponding author along with Saori Furuta, also with Berkeley Lab’s Life Sciences Division, of a paper describing this research in the Journal of Clinical Investigation (JCI). The paper is titled “FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice.” Other co-authors are Sun-Young Lee, Roland Meier, Marc Lenburg, Paraic Kenny and Ren Xu.

Therapeutic targeting of oncogenes can be an effective way to fight some cancers as evidenced in the successful use of EGFR-TKIs to fight lung cancer. However, EGFR-TKIs have not been effective for treating breast cancers. EGFR-TKIs work by blocking EGFR from adding a phosphate molecule to downstream signaling proteins, an action called phosphorylation that is a necessary step in the development of many types of cancer.

“We hypothesized that resistance to EGFR-TKIs originated, at least in part, from molecular alterations that activated phosphorylation signaling downstream of EGFRs,” Furuta says.

Using a unique three-dimensional cell culture assay based on phenotypic reversion that was originally developed by Bissell and her research group, the co-authors of the JCI paper screened for genes involved in EGFR-TKI resistance in both normal and cancerous human breast cell lines. They found that, while normal human breast tissue doesn’t produce FAM38A, the protein is highly expressed in cancerous tissue. This was true for every breast cancer cell line they examined, and was particularly pronounced in those cell lines that have been the most resistant to treatment with EGFR-TKIs. Further studies showed that FAM83A interacts with and causes phosphorylation of critical signaling proteins downstream of EGFRs, as the researchers hypothesized. This downstream phosphorylation would act to blunt or negate any therapeutic effects of EGFR-TKIs that took place further upstream.

The results of this research are consistent with clinical data showing that breast cancer patients with high levels of FAM83A have a significantly lower survival rate than patients with low levels of FAM83A. However, while Bissell, Furuta and their colleagues note that a number of questions about FAM83A and other members of the FAM83 protein family remain to be addressed, the importance of these proteins as potential drug targets for therapy seems clear.

“The beauty of this study is that it not only helps explain why some breast cancer patients are resistant to EGFR-TKIs, but it also reveals a whole new family of potential oncogenes that could be a target for all types of cancer, including breast cancer,” Bissell says.

Bissell says the results of this study also demonstrate the potential of using 3D phenotypic reversion assays as a new path to the discovery of more effective therapeutic drugs.

“Our 3D phenotypic reversion assay revealed the malignant phenotype, something that could not have been done with a 2D assay,” she says. “This is the first time we have used our assay to discover a potential target for cancer drugs, but it shows that an assay like ours can be a powerful tool for finding new targets and therapies.”

This research was primarily supported by the DOE Office of Science and the National Cancer Institute.

Lawrence Berkeley National Laboratory addresses the world’s most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab’s scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy’s Office of Science. For more, visit www.lbl.gov.

DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the Unites States, and is working to address some of the most pressing challenges of our time. For more information, please visit the Office of Science website at science.energy.gov.

Lynn Yarris | EurekAlert!
Further information:
http://www.lbl.gov
http://newscenter.lbl.gov/news-releases/2012/09/11/fam83a-oncogene-discovered/

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>