title: Comparative proteomic analysis of proliferating and functionally differentiated mammary epithelial cells.
abstract: 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.
authors.affiliation: Georg Speyer Haus, Paul-Ehrlich-Strasse 42-44, D-60596 Frankfurt am Main, Germany.
authors.forename: Sylvane
authors.initials: S
authors.lastname: Desrivières
authors.forename: Thorsten
authors.initials: T
authors.lastname: Prinz
authors.forename: Nahomi
authors.initials: N
authors.lastname: Castro-Palomino Laria
authors.forename: Markus
authors.initials: M
authors.lastname: Meyer
authors.forename: Gitte
authors.initials: G
authors.lastname: Boehm
authors.forename: Ute
authors.initials: U
authors.lastname: Bauer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schäfer
authors.forename: Thomas
authors.initials: T
authors.lastname: Neumann
authors.forename: Carrie
authors.initials: C
authors.lastname: Shemanko
authors.forename: Bernd
authors.initials: B
authors.lastname: Groner
mesh_terms: D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006019:Glycolysis; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011388:Prolactin / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D040901:Proteomics; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D003907:Dexamethasone; D011388:Prolactin; D004247:DNA; D046988:Proteasome Endopeptidase Complex