Premium
Retracted: A modified version of galectin‐9 induces cell cycle arrest and apoptosis of Burkitt and Hodgkin lymphoma cells
Author(s) -
Makishi Shoko,
Okudaira Taeko,
Ishikawa Chie,
Sawada Shigeki,
Watanabe Toshiki,
Hirashima Mitsuomi,
Sunakawa Hajime,
Mori Naoki
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07229.x
Subject(s) - xiap , survivin , cancer research , biology , lymphoma , cell cycle , null cell , cyclin d1 , cell growth , cell cycle checkpoint , apoptosis , microbiology and biotechnology , immunology , programmed cell death , cell culture , caspase , biochemistry , genetics
Summary The identification of galectin‐9 as a ligand for T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule‐3 (Tim‐3), expressed on T‐helper type‐1 (Th1) cells, has established the Tim‐3‐galectin‐9 pathway as a regulator of Th1 immunity. Whereas there is compelling evidence for the effects of galectin‐9 on T‐cell fate, limited information is available on the impact of galectin‐9 on B lymphocytes. We found that protease‐resistant galectin‐9, hG9NC(null), but not galectin‐1 or ‐8, prevented cell growth of malignant B cells, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). β‐galactoside binding was essential for galectin‐9‐induced cell growth suppression. hG9NC(null) induced cell cycle arrest by reducing the expression of cyclin D1, D2, B1, Cdk4, Cdc25C and c‐Myc, and apoptosis by reducing the expression of XIAP, c‐IAP2 and survivin. Most of the genes that encode these proteins are regulated by nuclear factor‐κB (NF‐κB), and constitutive activation of NF‐κΒ is a common characteristic of both types of malignancies. hG9NC(null) inhibited IκBα phosphorylation, resulting in suppression of NF‐κB. AP‐1 has also been implicated in the control of cell survival. hG9NC(null) inhibited the expression of JunD, resulting in the suppression of AP‐1. Our results suggest that hG9NC(null) is a potentially suitable agent for the management of BL and HL.