Association of nuclear membrane protein lamin B1 with necrosis and apoptosis in cell death induced by 5-fluoro-2'-deoxyuridine.
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.
Sato
Akira
A
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama, Japan.
Hiramoto
Akiko
A
Satake
Akito
A
Miyazaki
Eriko
E
Naito
Tomoharu
T
Wataya
Yusuke
Y
Kim
Hye-Sook
HS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology*; D045744:Cell Line, Tumor; D005467:Floxuridine / Q000494:pharmacology; D034921:Lamin Type B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009336:Necrosis; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D000970:Antineoplastic Agents; D034921:Lamin Type B; D034741:RNA, Small Interfering; D005467:Floxuridine