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Molecular & Cellular Proteomics 2:1039-1054, 2003.
© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Comparative Proteomic Analysis of Proliferating and Functionally Differentiated Mammary Epithelial Cells^*

Sylvane Desrivières, Thorsten Prinz, Nahomi Castro-Palomino Laria, Markus Meyer^,¶, Gitte Boehm, Ute Bauer, Jürgen Schäfer, Thomas Neumann, Carrie Shemanko^,||,** and Bernd Groner^,**,

From Georg Speyer Haus, Paul-Ehrlich-Strasse 42-44, D-60596 Frankfurt am Main, Germany and Proteome Sciences plc, Coveham House, Downside Bridge Road, Cobham, Surrey KT11 3EP, United Kingdom

Proliferation and differentiation of mammary epithelial cells are governed by hormonal stimuli, cell-cell, and cell-matrix interactions. Terminal differentiation of mammary epithelial cells depends upon the action of the lactogenic hormones, insulin, glucocorticoids, and prolactin that enable them to synthesize and secrete milk proteins. These differentiated cells are polarized and carry out vectorial transport of milk constituents across the apical plasma membrane. To gain additional insights into the mechanisms governing differentiation of mammary epithelial cells, we identified proteins whose expression distinguishes proliferating from differentiated mammary epithelial cells. For this purpose we made use of the HC11 mammary epithelial line, which is capable of differentiation in response to lactogenic hormones. Using two-dimensional gel electrophoresis and mass spectrometry, we found about 60 proteins whose expression levels changed in between these two differentiation states. Bioinformatic analysis revealed differential expression of cytoskeletal components, molecular chaperones and regulators of protein folding and stability, calcium-binding proteins, and components of RNA-processing pathways. The actin cytoskeleton is asymmetrically distributed in differentiated epithelial cells, and the identification of proteins involved in mRNA binding and localization suggests that asymmetry might in part be achieved by controlling cellular localization of mRNAs. The proteins identified provide insights into the differentiation of mammary epithelial cells and the regulation of this process.

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