Gal-3 is stimulated by gain-of-function p53 mutations and modulates chemoresistance in anaplastic thyroid carcinomas

Luca Lavra, Alessandra Ulivieri, Cinzia Rinaldo, Roberto Dominici, Marco Volante, Emidio Luciani, Armando Bartolazzi, Francesco Frasca, Silvia Soddu, Salvatore Sciacchitano

Research output: Contribution to journalArticle

Abstract

Galectin-3 (Gal-3) is an anti-apoptotic molecule of the j-galactoside-binding lectin family. Gal-3 is down-regulated by wt-p53 and this repression is required for p53-induced apoptosis. Since poorly differentiated thyroid carcinomas (PDTCs) and anaplastic thyroid carcinomas (ATCs) frequently harbour p53 mutations, we asked whether Gal-3 expression and activity could be influenced by such mutations in these tumours. We found a positive correlation between Gal-3 expression and p53 mutation in human thyroids and in thyroid carcinoma cell lines (TCCLs) harbouring different p53 mutations. Gal-3 was over-expressed in most ATCs and TCCLs, especially those with the most frequently detected p53 mutation (p 53R273H). Over-expression of p53 R273H in twop53-null cells (SAOS-2 and SW-1736) as well as in two wt- p53-carrying TCCLs (TPC-1 and K1), stimulated Gal-3 expression, while interference with p53R273H endogenous expression in ARO cells down-regulated Gal-3 expression. Conversely, over-expression of wt-p53 in ARO cells restored the inhibitory effect on Gal-3 expression. ARO cells are highly resistant to apoptosis and express both p53 and Gal-3, which are increased upon cisplatin treatment. Interference with Gal-3 expression in these cells stimulated their chemosensitivity. In conclusion, gain-of-function p53 mutant acquires the de novo ability to stimulate Gal-3 expression and to increase chemoresistance in ATCs.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalJournal of Pathology
Volume218
Issue number1
DOIs
Publication statusPublished - May 2009

Keywords

  • Anaplastic thyroid carcinoma (ATC)
  • Apoptosis
  • Chemoresistance
  • Clonogenic assay
  • Galectin-3
  • Human thyroid carcinoma cell lines
  • P53
  • Poorly differentiated thyroid carcinoma (PDTC)
  • Thyroid carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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