Regulation of the EphA2 tyrosine kinase in mammary epithelial cells
Abstract
The goal of the present study was to investigate how the EphA2 tyrosine kinase is regulated in non-transformed and transformed mammary epithelial cells. We found that the ErbB family of receptor tyrosine kinases, the Epidermal Growth Factor (EGF) family of ligands, the Mitogen Activated Protein Kinase pathway, and the microenvironment regulate EphA2 in mammary epithelial cells. Activation of ErbB receptors by EGF or neuregulin2β upregulated EphA2 expression in multiple cell lines. The importance of ErbB signaling was further supported by the finding that inhibition of the kinase activity of ErbB1 with specific chemical inhibitors downregulated EphA2 protein and mRNA expression. Similar results were obtained by specifically inhibiting MEK1, a signaling molecule frequently activated by ErbB signaling. In a different set of experiments, EphA2 expression was downregulated upon suspension of non-transformed and transformed but non-metastatic mammary epithelial cells in reconstituted basement membrane while metastatic MDA-MB-231 cells failed to downregulate EphA2. Chemical inhibition studies revealed that ErbB1 and MEK/ERK signaling also play important roles in the expression of EphA2 in a physiologically relevant microenvironment.
Degree
Ph.D.
Advisors
Kinch, Purdue University.
Subject Area
Cellular biology|Molecular biology
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