Proteome and transcriptome analysis of 5-fluoro-2'-deoxyuridine-induced cell death mechanisms.
5-Fluoro-2'-deoxyuridine (FUdR) inhibits thymidylate synthase. The inhibition of thymidylate synthase causes an imbalance of intracellular deoxyribonucleoside triphosphate (dNTP) pools which subsequently induced cell death. We have been investigated the molecular mechanisms of cell death in mouse mammary tumor FM3A cells, F28-7 strain and its mutant F28-7-A strain, after treated with FUdR. We have previously been reported that F28-7 strain induced DNA cleavage into chromosomal sized fragments and subsequently develop necrosis, but F28-7-A strain induced DNA cleavage into oligonucleosomal sized fragments and subsequently develop apoptosis after treated with FUdR. In this report, in order to understand the molecular mechanisms of regulate of two differential cell death necrosis and apoptosis, we identify cell death regulator by using proteome and transcriptome analysis. When compared with the proteome from F28-7 strain and F28-7-A strain, it was found that ten proteins were increased and six proteins were decreased in F28-7-A strain. Furthermore, transcriptome analysis shows that 127 genes were increased and 181 genes were decreased in F28-7-A strain. These differentially expressed proteins and genes were involved in various cellular processes such as cell cycle regulation, apoptosis, proliferation, and differentiation. These two techniques clarified numerous features in F28-7 strain and F28-7-A strain. Our results revealed that numerous features indicated the coordinated regulation of molecular networks from various aspects of necrosis or apoptosis at the proteome and transcriptome levels.
Sato
Akira
A
Faculty of Pharmaceutical Sciences, Okayama University, Tushima, Okayama 700-8530, Japan.
Miyazaki
Eriko
E
Satake
Akito
A
Hiramoto
Akiko
A
Hiraoka
Osamu
O
Miyake
Tsuyoshi
T
Kim
Hye-Sook
HS
Wataya
Yusuke
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis; D045744:Cell Line, Tumor; D005467:Floxuridine / Q000633:toxicity*; D020869:Gene Expression Profiling; D051379:Mice; D009336:Necrosis; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D014158:Transcription, Genetic / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic; D020543:Proteome; D005467:Floxuridine