Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice

Fumiyasu Okazaki, Matsunaga Naoya, Hiroyuki Okazaki, Naoki Utoguchi, Ryo Suzuki, Kazuo Maruyama, Koyanagi Satoru, Shigehiro Ohdo

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The abundance of cell surface levels of transferrin receptor 1 (TfR1), which regulates the uptake of iron-bound transferring, correlates with the rate of cell proliferation. Because TfR1 expression is higher in cancer cells than in normal cells, it offers a target for cancer therapy. In this study, we found that the expression of TfR1 in mouse colon cancer cells was affected by the circadian organization of the molecular clock. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop, in which CLOCK and BMAL1 are positive regulators and the Period (Per), Cryptochrome (Cry), and Dec genes act as negative regulators. TfR1 in colon cancer-bearing mice exhibited a 24-hour rhythm in mRNA and protein levels. Luciferase reporter analysis and chromatin immunoprecipitation experiments suggested that the clock-controlled gene c-MYC rhythmically activated the transcription of the TfR1 gene. Platinum incorporation into tumor DNA and the antitumor efficacy of transferrin-conjugated liposome-delivered oxaliplatin could be enhanced by drug administration at times when TfR1 expression increased. Our findings suggest that the 24-hour rhythm of TfR1 expression may form an important aspect of strategies for TfR1-targeted cancer therapy.

Original languageEnglish
Pages (from-to)6238-6246
Number of pages9
JournalCancer Research
Volume70
Issue number15
DOIs
Publication statusPublished - Aug 1 2010

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Transferrin Receptors
Circadian Rhythm
Colonic Neoplasms
Gene Expression
oxaliplatin
Neoplasms
Cryptochromes
Genes
Chromatin Immunoprecipitation
Transferrin
Platinum
Luciferases
Liposomes
Iron
Cell Proliferation
Messenger RNA
DNA
Therapeutics
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice. / Okazaki, Fumiyasu; Naoya, Matsunaga; Okazaki, Hiroyuki; Utoguchi, Naoki; Suzuki, Ryo; Maruyama, Kazuo; Satoru, Koyanagi; Ohdo, Shigehiro.

In: Cancer Research, Vol. 70, No. 15, 01.08.2010, p. 6238-6246.

Research output: Contribution to journalArticle

Okazaki, Fumiyasu ; Naoya, Matsunaga ; Okazaki, Hiroyuki ; Utoguchi, Naoki ; Suzuki, Ryo ; Maruyama, Kazuo ; Satoru, Koyanagi ; Ohdo, Shigehiro. / Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice. In: Cancer Research. 2010 ; Vol. 70, No. 15. pp. 6238-6246.
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