Abstract
Elevated levels of protein tyrosine phosphorylation contribute to a malignant phenotype, although the tyrosine kinases that are responsible for this signaling remain largely unknown. Here we report increased levels of the EphA2 (ECK) protein tyrosine kinase in clinical specimens and cell models of breast cancer. We also show that EphA2 overexpression is sufficient to confer malignant transformation and tumorigenic potential on nontransformed (MCF-10A) mammary epithelial cells. The transforming capacity of EphA2 is related to the failure of EphA2 to interact with its cell-attached ligands. Interestingly, stimulation of EphA2 reverses the malignant growth and invasiveness of EphA2-transformed cells. Taken together, these results identify EphA2 as a powerful oncoprotein in breast cancer.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by the American Cancer Society, NIH, Department of Defense Breast Cancer Research Program, and the Howard Hughes Medical Institute (N. D. Z.).
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↵2 To whom requests for reprints should be addressed, at Department of Basic Medical Sciences, 1246 Lynn Hall, Purdue University, West Lafayette, Indiana 47907-1246.
- Received August 10, 2000.
- Accepted January 3, 2001.
- ©2001 American Association for Cancer Research.
Volume 61, Issue 5
