Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

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

Gal‐3 is stimulated by gain‐of‐function p53 mutations and modulates chemoresistance in anaplastic... Galectin‐3 (Gal‐3) is an anti‐apoptotic molecule of the β‐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 (p53R273H). Over‐expression of p53R273H 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 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. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Pathology Wiley

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

Download PDF
10 pages

Loading next page...
 
/lp/wiley/gal-3-is-stimulated-by-gain-of-function-p53-mutations-and-modulates-UblDstY6jw

References (43)

Publisher
Wiley
Copyright
Copyright © 2009 Wiley Subscription Services
ISSN
0022-3417
eISSN
1096-9896
DOI
10.1002/path.2510
pmid
19199318
Publisher site
See Article on Publisher Site

Abstract

Galectin‐3 (Gal‐3) is an anti‐apoptotic molecule of the β‐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 (p53R273H). Over‐expression of p53R273H 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 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. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Journal

The Journal of Pathology – Wiley

Published: Jan 1, 2009

Keywords: ; ; ; ; ; ; ; ;

There are no references for this article.