RT Journal Article
SR Electronic
T1 Circadian Rhythm of Transferrin Receptor 1 Gene Expression Controlled by c-Myc in Colon Cancer–Bearing Mice
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 6238
OP 6246
DO 10.1158/0008-5472.CAN-10-0184
VO 70
IS 15
A1 Okazaki, Fumiyasu
A1 Matsunaga, Naoya
A1 Okazaki, Hiroyuki
A1 Utoguchi, Naoki
A1 Suzuki, Ryo
A1 Maruyama, Kazuo
A1 Koyanagi, Satoru
A1 Ohdo, Shigehiro
YR 2010
UL http://cancerres.aacrjournals.org/content/70/15/6238.abstract
AB 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. Cancer Res; 70(15); 6238–46. ©2010 AACR.