title: Nuclear localization of Galectin-3 in transformed thyroid cells: a role in transcriptional regulation.
abstract: The differential proteomic approach (2D gel analysis coupled to MALDI-MS analysis) of nuclear proteins can provide an extremely useful tool to understand control of cell proliferation and differentiation. In order to identify possible markers of dedifferentiation between normal and cancerous thyroid cells, we used a differential proteomics approach by comparing nuclear extracts from the normal rat thyroid cell line FRTL-5 and the completely undifferentiated Ki-mol cell line, obtained by transformation with the Ki-ras oncogene. Galectin-3 (Gal-3) was identified as highly expressed, in the nuclear compartment, only in the transformed cell line. By using different human cancer cell lines, we showed that Gal-3 is maximally expressed in nuclei of papillary cancer cells. We focused on the functional relationship existing between Gal-3 and the thyroid-specific transcription factor TTF-1, whose expression is maintained in papillary cancer where it can contribute to the proliferating status. By using gel-retardation and transient tranfection assays, we demonstrate that Gal-3 upregulates the TTF-1 transcriptional activity. GST-pulldown experiments demonstrate the occurrence of interaction between Gal-3 and TTF-1 homeodomain. Since several lines of evidence suggest a role for Gal-3 in controlling proliferation and tumor progression in thyroid cancer, the stimulatory activity played by Gal-3 over TTF-1 would account for a possible molecular mechanism through which the galectin controls proliferation in thyroid cells.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, P.le Kolbe 1, Università degli Studi di Udine, 33100 Udine, Italy.
authors.forename: Igor
authors.initials: I
authors.lastname: Paron
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Alex
authors.initials: A
authors.lastname: Pines
authors.forename: Angela
authors.initials: A
authors.lastname: Bachi
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.forename: Maura
authors.initials: M
authors.lastname: Pandolfi
authors.forename: Luigi
authors.initials: L
authors.lastname: Ledda
authors.forename: Carla
authors.initials: C
authors.lastname: Di Loreto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tell
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D037502:Galectin 3 / Q000378:metabolism* / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D009687:Nuclear Proteins / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013961:Thyroid Gland / Q000166:cytology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D037502:Galectin 3; C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D009841:Oligonucleotides; D011994:Recombinant Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D005982:Glutathione Transferase