TY - JOUR
T1 - Association of nuclear membrane protein lamin B1 with necrosis and apoptosis in cell death induced by 5-fluoro-2′-deoxyuridine
AU - Sato, Akira
AU - Hiramoto, Akiko
AU - Satake, Akito
AU - Miyazaki, Eriko
AU - Naito, Tomoharu
AU - Wataya, Yusuke
AU - Kim, Hye Sook
N1 - Funding Information:
Received 24 January 2008; accepted 1 February 2008. The authors thank Dr. Hikoya Hayatsu (Faculty of Pharmaceutical Sciences, Okayama University) for helpful discussions. This research was partly supported by the Ministry of Education, Culture, Sports, Science and Technology for Exploratory Research (18659029, Y. W.). Address correspondence to Hye-Sook Kim, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan. E-mail: hskim@cc.okayama-u.ac.jp
PY - 2008/5
Y1 - 2008/5
N2 - We report that anticancer 5-fluoro-2′-deoxyuridine (FUdR) shows cytotoxicity against mouse cancer cell line FM3A, using a progeny clone F28-7 and its variant F28-7-A. In this process, the cell-death morphology is different between F28-7 and F28-7-A cells, that is, necrosis in F28-7 but apoptosis in F28-7-A cells. In the proteomic analysis of these cells before their exposure to FUdR, the nuclear inner-membrane protein lamin B1 is up-regulated in F28-7 but not in F28-7-A, suggesting that lamin B1 may possess a function to regulate the morphology of cell-death. A knockdown of lamin B1 expression in F28-7 cells was performed by use of the small interfering RNA technique, resulting in a decrease of the lamin B1-expression level down to the level in F28-7-A. Remarkably, the FUdR-induced death morphology of this knocked-down F28-7 was apoptosis, definitely different from the necrosis that occurs in the FUdR-treated original F28-7. Thus, the swelling feature for the necrosis was no longer observable, and instead cell shrinkage typical of apoptosis took place in almost all the cells examined. This finding suggests a new role for lamin B1 as a regulator in cell death.
AB - We report that anticancer 5-fluoro-2′-deoxyuridine (FUdR) shows cytotoxicity against mouse cancer cell line FM3A, using a progeny clone F28-7 and its variant F28-7-A. In this process, the cell-death morphology is different between F28-7 and F28-7-A cells, that is, necrosis in F28-7 but apoptosis in F28-7-A cells. In the proteomic analysis of these cells before their exposure to FUdR, the nuclear inner-membrane protein lamin B1 is up-regulated in F28-7 but not in F28-7-A, suggesting that lamin B1 may possess a function to regulate the morphology of cell-death. A knockdown of lamin B1 expression in F28-7 cells was performed by use of the small interfering RNA technique, resulting in a decrease of the lamin B1-expression level down to the level in F28-7-A. Remarkably, the FUdR-induced death morphology of this knocked-down F28-7 was apoptosis, definitely different from the necrosis that occurs in the FUdR-treated original F28-7. Thus, the swelling feature for the necrosis was no longer observable, and instead cell shrinkage typical of apoptosis took place in almost all the cells examined. This finding suggests a new role for lamin B1 as a regulator in cell death.
KW - 5-Fluoro-2′-deoxyuridine
KW - Apoptosis
KW - Lamin B1
KW - Necrosis
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U2 - 10.1080/15257770802086864
DO - 10.1080/15257770802086864
M3 - Article
C2 - 18569782
AN - SCOPUS:45849085772
VL - 27
SP - 433
EP - 438
JO - Nucleosides, Nucleotides and Nucleic Acids
JF - Nucleosides, Nucleotides and Nucleic Acids
SN - 1525-7770
IS - 5
ER -