Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine

Akira Sato, Akiko Hiramoto, Yusuke Uchikubo, Eriko Miyazaki, Akito Satake, Tomoharu Naito, Osamu Hiraoka, Tsuyoshi Miyake, Hye-Sook Kim, Yusuke Wataya

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

5-Fluoro-2′-deoxyuridine (FUdR), a potent anticancer agent, exerts its effects by inhibiting thymidylate synthase, an essential machinery for DNA synthesis in cell proliferation. Also, cell death is caused by FUdR, primarily due to an imbalance in the nucleotide pool resulting from this enzyme inhibition. We have investigated the cancer cell death induced by FUdR, focusing on its molecular mechanisms. Using mouse mammary tumor FM3A cell lines, the original clone F28-7 and its variant F28-7-A cells, we previously reported an interesting observation that FUdR induces a necrotic morphology in F28-7, but induces, in contrast, an apoptotic morphology in F28-7-A cells. In the present study, to understand the molecular mechanisms underlying these differential cell deaths, i.e., necrosis and apoptosis, we investigated the gene expression changes occurring in these processes. Using the cDNA microarray technology, we found 215 genes being expressed differentially in the necrosis and apoptosis. Further analysis revealed differences between these cell lines in terms of the expressions of both a cluster of heat shock protein (HSP)-related genes and a cluster of apoptosis-related genes. Notably, inhibition of HSP90 in F28-7 cells caused a shift from the FUdR-induced necrosis into apoptosis. These findings are expected to lead to a better understanding of this anticancer drug FUdR for its molecular mechanisms and also of the general biological issue, necrosis and apoptosis.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalGenomics
Volume92
Issue number1
DOIs
Publication statusPublished - Jul 2008

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Transcriptome
Necrosis
Apoptosis
Cell Death
Thymidylate Synthase
Multigene Family
Heat-Shock Proteins
Oligonucleotide Array Sequence Analysis
Tumor Cell Line
Antineoplastic Agents
Genes
5-fluoro-2'-deoxyuridine
Nucleotides
Clone Cells
Cell Proliferation
Observation
Breast Neoplasms
Technology
Gene Expression
Cell Line

Keywords

  • 5-Fluoro-2′-deoxyuridine
  • Apoptosis
  • Cell death
  • Gene expression profile
  • Microarray analysis
  • Necrosis

ASJC Scopus subject areas

  • Genetics

Cite this

Sato, A., Hiramoto, A., Uchikubo, Y., Miyazaki, E., Satake, A., Naito, T., ... Wataya, Y. (2008). Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine. Genomics, 92(1), 9-17. https://doi.org/10.1016/j.ygeno.2008.02.002

Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine. / Sato, Akira; Hiramoto, Akiko; Uchikubo, Yusuke; Miyazaki, Eriko; Satake, Akito; Naito, Tomoharu; Hiraoka, Osamu; Miyake, Tsuyoshi; Kim, Hye-Sook; Wataya, Yusuke.

In: Genomics, Vol. 92, No. 1, 07.2008, p. 9-17.

Research output: Contribution to journalArticle

Sato, A, Hiramoto, A, Uchikubo, Y, Miyazaki, E, Satake, A, Naito, T, Hiraoka, O, Miyake, T, Kim, H-S & Wataya, Y 2008, 'Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine', Genomics, vol. 92, no. 1, pp. 9-17. https://doi.org/10.1016/j.ygeno.2008.02.002
Sato A, Hiramoto A, Uchikubo Y, Miyazaki E, Satake A, Naito T et al. Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine. Genomics. 2008 Jul;92(1):9-17. https://doi.org/10.1016/j.ygeno.2008.02.002
Sato, Akira ; Hiramoto, Akiko ; Uchikubo, Yusuke ; Miyazaki, Eriko ; Satake, Akito ; Naito, Tomoharu ; Hiraoka, Osamu ; Miyake, Tsuyoshi ; Kim, Hye-Sook ; Wataya, Yusuke. / Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine. In: Genomics. 2008 ; Vol. 92, No. 1. pp. 9-17.
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