Navigation Links
Penn researchers identify potential target for breast cancer therapy
Date:12/22/2010

PHILADELPHIA Overexpression or hyperactivation of ErbB cell-surface receptors drives the growth of many breast cancers. Drugs, like Herceptin, that block the receptors' signals halt tumor progression in some patients. However, not all patients' tumors respond, with some becoming resistant over time. Different drugs that interfere with other steps in the signaling pathway may improve the response of patients, yet little is known about these molecules.

Now, Marcelo G. Kazanietz, PhD, professor of Pharmacology at the University of Pennsylvania School of Medicine and colleagues, report that a protein called P-Rex1 is crucial for signal transmission from ErbB receptors. What's more, they found that P-Rex1 is overexpressed in nearly 60 percent of breast cancer samples tested and patients whose tumors express P-Rex1 were more likely to develop metastasis, compared with those whose tumors did not express P-Rex1.

"We identified a downstream target of the ErbB receptors which seems to be crucial for cancer cell proliferation, migration, and metastasis," Kazanietz says. "Understanding how this pathway works should allow us to find new drugs or therapeutic approaches in the future."

The team's research is featured on the cover of the December 22 issue of Molecular Cell.

A Well-Known Family

The ErbB family of receptors is well known in the cancer world. The family includes the epidermal growth factor receptor (EGFR, also known as ErbB1); ErbB2 (also known as HER2/neu), which is the target of Herceptin; as well as ErbB and ErbB4.

Previous work from Kazanietz and others suggested the receptors might rely on small proteins in the Rac pathway to help transmit their signal. To find out if that was the case, Kazanietz and colleagues examined human breast cancer cell lines and found that one Rac pathway protein, P-Rex1, is overexpressed in numerous cell lines compared with normal mammary cells. The team also found that P-Rex1 is present in some breast tumors, particularly those that express the Her2/neu receptor or estrogen receptor and belong to the luminal subtype.

"We found that about two-thirds of the patient samples had very high levels of P-Rex1 expression in tumor cells in their lymph nodes," Kazanietz says. "There seems to be a correlation between P-Rex1 expression in the tumor cells and the capacity of these cells to metastasize. And since P-Rex1 is likely to be essential for cell migration and migration is essential for metastasis, we believe blocking this pathway could reduce the risk of metastasis."

P-Rex1 may be important for several other cancer-promoting pathways. For example, estrogen-receptor signaling also appears to rely on P-Rex1, which means that targeted inhibitors of P-Rex1 might improve responses to anti-estrogen therapies such as tamoxifen.

The authors also found that P-Rex1 is also used by another receptor, CXCR4, which has recently shown up in many cancer studies. Despite being used in numerous pathways during cancerous growth, P-Rex1 is not expressed in many normal tissues. "That gives us a very good target. It is really cancer specific," Kazanietz says. "What's more, as P-Rex1 is expressed in some subtypes of breast tumors, it may be an excellent prototype for future personalized medicine."

Preclinical data from other groups supports the importance of the Rac pathway in cancer, according to Kazanietz. And small molecule inhibitors that block proteins in the Rac pathway appear to have strong anti-cancer effects in model systems, though their use in patients still needs to be tested.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Researchers Turn White Fat to Energy-Burning Brown Fat in Mice
2. Finnish researchers find a compound that prevents the growth of prostate cancer cells
3. Ben-Gurion U. researchers: High resistance rates among acute otitis media pathogens in children
4. Breast inflammation is key to cancer growth, Kimmel Cancer Center researchers say
5. Researchers discover new signaling pathway linked to inflammatory disease
6. UCI researchers find novel memory-enhancing mechanism in brain
7. Researchers make critical leukemia stem cell discovery
8. U-M researchers discover way to block neurodegeneration in an adult form of Fragile X syndrome
9. Leibniz Prize 2011: 10 researchers awarded €2.5 million ($3.3 million) each
10. Researchers Turn Stem Cells Into Intestinal Tissue in Lab
11. Expert analysis of HER2 tests reveals issues with reliability, Mayo Clinic researchers say
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Penn researchers identify potential target for breast cancer therapy
(Date:2/23/2017)... ... February 23, 2017 , ... On February 22, ... a letter to withdraw previous guidance issued by the Obama Administration requiring ... issued in May 2016 by the Obama Administration came in response to a ...
(Date:2/23/2017)... ... February 23, 2017 , ... The Lymphoma Research Foundation (LRF) ... and serving the lymphoma community through a comprehensive series of education programs, outreach ... in Miami Beach to host its Swirl: Miami Wine Tasting Event on March ...
(Date:2/23/2017)... (PRWEB) , ... February 23, 2017 , ... The American ... for ACPA’s 74th Annual Meeting. KLS is a longtime supporter of the event. ... an exhibitor and Platinum Sponsor," said Dr. Bob Havlik, 2017 ACPA President. "KLS Martin ...
(Date:2/23/2017)... ... February 23, 2017 , ... Hamlin Dental Group and Dr. Hamid Reza, ... raffle. Throughout the month of February, patients who visit Hamlin Dental Group will receive ... dinner for two at the Cheesecake Factory. , Tickets are available for routine ...
(Date:2/23/2017)... ... February 23, 2017 , ... ... content provider for the National Institute for Health and Care Excellence ... organizations in the National Health Service (NHS) to search, order and purchase medical ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... 2017  Directors from Pharma To Market Pty Ltd and Ador ... resulting in the founding of Pharma To Market Pte Ltd, based ... are pleased to announce their expansion into Asia ... . The company are delighted to appoint Joelle Chia ... Singapore based entity. Joelle brings with her an ...
(Date:2/24/2017)... Feb. 23, 2017  The particle counters market ... 2021 from USD 275.9 million in 2016, at ... full report: http://www.reportlinker.com/p04718602-summary/view-report.html The ... pharmaceutical R&D, and growth in manufacturing industries in ... growth for particle counters. On the other hand, ...
(Date:2/24/2017)... Research and Markets has announced the addition of the ... report to their offering. ... The latest research Urinary Incontinence Drugs Price Analysis and ... global Urinary Incontinence market. The research answers the following questions: ... for Urinary Incontinence and their clinical attributes? How are they positioned ...
Breaking Medicine Technology: