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Regulation of anoikis by engagement of Btg2/TIS21 expression in serum deprived promyelocytic leukemia HL-60 cells

Imran, Muhammad; Lim, In Kyoung
Department of Biochemistry & Molecular Biology
Human BTG2 (B-cell translocation gene 2), an ortholog mouse TIS21 (12-O-tetradecanoyl phorbol-13-acetate inducible sequence 21), and rat PC3, is a tumor suppressor that belongs to antiproliferative gene family. Btg2/TIS21 has been implicated in a variety of biological processes such as cell cycle regulation, apoptosis, development and differentiation. We have previously established a role of TIS21/BTG2 in retinoic acid induced differentiation of leukemic cells. Here we report the involvement of BTG2/TIS21 in serum depletion-induced cells adhesion, apoptosis or anoikis like behavior in HL-60. Expression of Btg2 was up-regulated in acute promyelocytic leukemia HL-60 cells but not in myelomonocytic U937 cells under serum deprived condition which induced HL-60 cells adherence to culture dishes for 1 hour and then successive floating to cultured media. The adherent cells revealed actin cytoskeleton remodeling and increase of ROS generation that in turn led to cells death. On the other hand coating culture dishes with poly-HEMA significantly blocked cells adhesion and Btg2 up-regulation suggesting that cell to ECM communication might signal to cell death via Btg2 induction which in turn regulate cell adhesion regulating proteins. Our study suggests that engagement of Btg2 expression triggered by serum deprivation possibly regulate cell death through the regulation of actin remodeling activities which in turn regulates anoikis phenotype in leukemic HL-60 cells. We are going to discuss about the regulation of cell adhesion molecules and actin remodeling activities by engaged Btg2 expression in leukemic cells.
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