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01-12-2011 | Research Paper

Galectin-3 germline variant at position 191 enhances nuclear accumulation and activation of β-catenin in gastric cancer

Authors: Seok-Jun Kim, Ji-Young Shin, Teak-Chin Cheong, Il-Ju Choi, Yeon Su Lee, Seok Hee Park, Kyung-Hee Chun

Published in: Clinical & Experimental Metastasis | Issue 8/2011

Abstract

Mutation of galectin-3 at position 191 (rs4644) substituting proline to histidine (gal-3H⁶⁴) resulted in the acquisition of resistance to drug-induced apoptosis by breast cancer cells. This study employed gastric cancer cells and patient tissues in attempts to elucidate how and why this mutation in galectin-3 (gal-3H⁶⁴) enhances cancer progression, compared to wild type galectin-3 (gal-3P⁶⁴). First, we prepared lenti-virus constructs containing gal-3P⁶⁴, gal-3H⁶⁴ and LacZ, and used them to infect galectin-3 null SNU-638 cells. We found that gal-3H⁶⁴ over-expression increases gastric cancer cell growth more than gal-3P⁶⁴ or LacZ over-expression. Also, gal-3H⁶⁴ over-expression conferred more resistance to cisplatin or 5-FU induced cytotoxicity than gal-3P⁶⁴. Gal-3H⁶⁴ also enhanced nuclear accumulation of β-catenin as well as increased expression of TCF-4 target genes, such as fascin-1 and c-Myc through the augmented promoter binding activity of TCF-4, than gal-3P⁶⁴. We also demonstrated stronger staining of β-catenin and galectin-3 in malignant tissues from gastric cancer patients with mutated galectin-3 at position 191 (gal-3 191) (A/A) (H⁶⁴) and greater localization in the nucleus than in gal-3 191 A/C (P⁶⁴) cancer patients. Taken together, we elucidated in this study that germline variant of gal-3H⁶⁴ increases nuclear accumulation of β-catenin and promotes TCF transcriptional activity and enhances more the galectin-3’s role in gastric cancer progression.

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Title: Galectin-3 germline variant at position 191 enhances nuclear accumulation and activation of β-catenin in gastric cancer
Authors: Seok-Jun Kim
Ji-Young Shin
Teak-Chin Cheong
Il-Ju Choi
Yeon Su Lee
Seok Hee Park
Kyung-Hee Chun
Publication date: 01-12-2011
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 8/2011
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-011-9406-8

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