title: Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice.
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.
authors.affiliation: Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Okazaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsunaga
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Utoguchi
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Satoru
authors.initials: S
authors.lastname: Koyanagi
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Ohdo
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010984:Platinum / Q000493:pharmacokinetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics*; D014168:Transferrin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D004273:DNA, Neoplasm; D008081:Liposomes; C489428:Myc protein, mouse; D009944:Organoplatinum Compounds; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D014168:Transferrin; D000077150:Oxaliplatin; D010984:Platinum