Gal‐3 is stimulated by gain‐of‐function p53 mutations and modulates chemoresistance in anaplastic thyroid carcinomas
Citations Over TimeTop 25% of 2008 papers
Abstract
Galectin-3 (Gal-3) is an anti-apoptotic molecule of the beta-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 (p53(R273H)). Over-expression of p53(R273H) in two p53-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 p53(R273H) 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.
Related Papers
- → Viral pathogens and the advantage of sex in the perennial grass Anthoxanthum odoratum(1997)40 cited
- → Cloning and Characterization of Rat BAT3 cDNA(1999)20 cited
- → Anthoxanthum Mosaic Virus(1970)6 cited
- → HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53(2007)127 cited
- → Ecological and evolutionary importance of neighbors in the grass Anthoxanthum odoratum(1990)20 cited