Nuclear localization of Galectin-3 in transformed thyroid cells: A role in transcriptional regulation

Igor Paron, Andrea Scaloni, Alex Pines, Angela Bachi, Fu-Tong Liu, Cinzia Puppin, Maura Pandolfi, Luigi Ledda, Carla Di Loreto, Giuseppe Damante, Gianluca Tell

Research output: Contribution to journalArticle

87 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)545-553
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume302
Issue number3
DOIs
StatePublished - Mar 14 2003
Externally publishedYes

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Keywords

  • Differential proteomics
  • Differentiation
  • Galectin-3
  • Thyroid
  • Transcriptional regulation
  • TTF-1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Paron, I., Scaloni, A., Pines, A., Bachi, A., Liu, F-T., Puppin, C., Pandolfi, M., Ledda, L., Di Loreto, C., Damante, G., & Tell, G. (2003). Nuclear localization of Galectin-3 in transformed thyroid cells: A role in transcriptional regulation. Biochemical and Biophysical Research Communications, 302(3), 545-553. https://doi.org/10.1016/S0006-291X(03)00151-7