Overexpression of the protein EphA2 in aggressive breast cancer is common, and generally leads to poor outcome for the patient. However, the function of Eph2A in cancer progression is controversial, with conflicting evidence suggesting both pro- and anti-cancer roles for the protein.
In a new study, Jin Chen and colleagues from Vanderbilt University School of Medicine, Nashville, have presented evidence that the role Eph2A in breast cancer is highly context dependent.
EphA2 expression was eliminated in two different mouse models of breast cancer that mimic the progression of human tumors through the various stages. MMTV-Neu is a mouse model for overexpression of NEU, a cancer-causing gene (oncogene) that is overexpressed in about 30% of human breast cancer cases.
In contrast, the MMTV--PyV-mT mouse models multistep progression of human breast cancers by activation of a number of oncogenes. The researchers found that EphA2 deficiency in MMTV-Neu mice impaired both the initiation of tumor growth and the progression of metastasis.
Further analysis of mouse cells revealed that the presence of EphA2 enhanced tumor growth and movement by binding Neu. In addition, treatment of MMTV-Neu mice with an anti-EphA2 therapy reduced tumor volume. In contrast, EphA2 deletion had no noticeable effect on cancer progression in the MMTV-PyV-mT mice.
The authors therefore concluded that EphA2 interacts with Neu to enhance tumor progression, and might be a novel target for treating individuals with tumors dependent on Neu signaling.
Journal article: The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. Journal of Clinical Investigation. Dec 13, 2007.
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
Cite This Page: