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 fo
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine