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Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47905 [N. D. Z., J. W-D., J. S., M. S. K.]; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 [R. K. H., M. J. B.]; Department of Biological Chemistry, University of California-Davis, Sacramento, California 95817 [D. R., H-J. K.]; and Rammelkamp Center for Research, Case Western Reserve University, Cleveland, Ohio 44109 [H. M., B. W.]
Purpose: There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers.
Experimental Design: We report here the isolation and initial characterization of a spontaneously arising variant of MCF-10A cells, NeoST, which provides a new model to study cell adhesion and signal transduction in breast cancer.
Results: NeoST cells recapitulate important biological and biochemical features of metastatic breast cancer, including anchorage-independent growth, invasiveness in three-dimensional reconstituted membranes, loss of E-cadherin expression, and increased tyrosine kinase activity. A comprehensive analysis of tyrosine kinase expression revealed overexpression or functional activation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells.
Conclusions: MCF-10A and these new derivatives provide a genetically matched model to study defects in cell adhesion and signaling that are relevant to cellular behaviors that often typify aggressive breast cancer cells.
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