Induction of Cellular Induction Senescence by BTG2_(TIS21/PC3) Gene in Huh7 Hepatocellular carcinoma Cells

TIS21^(BTG2/PC3) regulates G1-S and G2-M progressions of cell division cycle through the inhibition of G1 phase cyclin biosynthesis, and the delayed degradations of cycin B1 and cyclin A, respectively. Therefore, we earlier suggested that TIS21 might play a role as a pan-cell cycle regulator and an important factor for cellular senescence. However, there has been no experimental evidence to confirm TIS21 as a regulator of cellular senescence. In this study, we observed the changes of TIS21 expression in the replicative senescence of human diploid fibroblast (HDF) cells. Furthermore, when we treated Huh7 hepatoma cells with H₂O₂, the expression of BTG2 mRNA was highly induced, accompanied with senescence phenotypes. To investigate a role of TIS21 in the process of cellular senescence, Huh7 cells were transfected with TIS21 cDNA construct. The followings were observed; Growth of the Huh7 cells was significantly decreased, cell shapes were changed from small and cylindrical young cell-like to large and flat cells, and percentages of the cells with senescence associated (SA)-β-galactosidase activity were significantly increased after adeno-TIS21-HA virus infection to Huh7 cells. Mouse embryonic fibroblast (MEF) cells derived from TIS21+/+ and TIS21-/- mice showed that the SA-β-gal activity was significantly increased in TIS21+/+ MEF cells of passage 10 compared with that of TIS21-/- MEF cells. And growth of the MEF cells was significantly increased in TIS21-/- MEF cells of passage 3 compared with that of TIS21+/+ MEF cells. Furthermore, over-expression of TIS21 induced MnSOD expression and decreased mitochondrial membrane potential (MMP) difference in Huh7 cells after combined treatment with doxorubicin. The above data suggest that TIS21 might induce cellular senescence phenotypes both in HDF and Huh7 cells.

Author dc:creator

• 강, 소영

Contributors dc:contributor

• 임, 인경
• 대학원 의학과
• 200624277

• BTG2_(TIS21/PC3)
• 세포노화유도
• HDF
• Huh7
• induced-cellular senescence

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000006666
000000006666

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1840