Navigation Links
Protein linked to therapy resistance in breast cancer

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) to the resistance of breast cancer 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."


Contact: Lynn Yarris
DOE/Lawrence Berkeley National Laboratory

Related medicine news :

1. Well-known protein reveals new tricks
2. Binding sites for LIN28 protein found in thousands of human genes
3. Immune system protein could explain pancreatitis
4. In Diabetes, Any Protein in Urine May Signal Heart Risk
5. Protein impedes microcirculation of malaria-infected red blood cells
6. Protein found to regulate red blood cell size and number
7. Toward medicines that recruit the bodys natural disease-fighting proteins
8. New laboratory test assesses how DNA damage affects protein synthesis
9. Stem cells can become anything - but not without this protein
10. Alzheimer protein seems to slow down neurotransmitter production
11. Stanford/Intel study details power of new chip to diagnose disease, analyze protein interactions
Post Your Comments:
Related Image:
Protein linked to therapy resistance in breast cancer
(Date:11/27/2015)... ... November 27, 2015 , ... The moment you stop improving ... only fulfilling the needs of advisers and clients but going above and beyond ... top-tier customer service. However, there's always room for improvement, which is why the ...
(Date:11/27/2015)... ... November 27, 2015 , ... Avid collector, Andrew Hawley from Vintage Rock Posters, ... posters. This is one of Joplin's most famous and beautiful concert posters. The concert ... Michigan in Ann Arbor. The According to Hawley, "It is hard to believe that ...
(Date:11/26/2015)... ... 26, 2015 , ... Somu Sivaramakrishnan announced today that he ... now offers travelers, value and care based Travel Services, including exclusive pricing on ... as, cabin upgrades and special amenities such as, shore excursions, discounted fares, travel ...
(Date:11/26/2015)... ... November 26, 2015 , ... Pixel Film Studios brings Final ... ProTrailer: Vintage. This newly styled ProTrailer pack comes with 30 all-new vintage-inspired designs, ... giving users limitless opportunities to stylize and create designs quickly and easily, all ...
(Date:11/25/2015)... ... ... The holiday season is jam-packed with family dinners, parties ... is of the utmost importance. Whether you are cooking at home for the ... try this holiday season. , Turkey Croquettes ,     Ingredients: , ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... India , November 26, 2015 ... --> adds ... Report" and "Investigation Report on China ... and 2021 forecasts data and information ... . ...
(Date:11/26/2015)... 26, 2015 ... of the  "2016 Future Horizons and ... Surface Marker Testing Market: Supplier Shares, ... their offering.  --> ... the  "2016 Future Horizons and Growth ...
(Date:11/25/2015)...  The American Academy of Pediatrics (AAP), American ... March of Dimes cheered today,s signature into law ... of 2015 (S.799), which takes much-needed strides ... to drugs, such as opioids, and to improve ... organizations have worked together leading advocacy efforts for ...
Breaking Medicine Technology: