The Impact of HIF1α on the Per2 Circadian Rhythm in Renal Cancer Cell Lines

被引:34
作者
Okabe, Takashi [1 ]
Kumagai, Megumi [2 ,3 ]
Nakajima, Yoshihiro [4 ]
Shirotake, Suguru [1 ]
Kodaira, Kiichiro [1 ]
Oyama, Masafumi [1 ]
Ueno, Munehisa [1 ]
Ikeda, Masaaki [2 ,3 ]
机构
[1] Saitama Med Univ, Int Med Ctr, Dept Urooncol, Saitama, Japan
[2] Saitama Med Univ, Dept Physiol, Saitama, Japan
[3] Saitama Med Univ, Res Ctr Genom Med, Project Res Div, Mol Clock Project, Saitama, Japan
[4] Natl Inst Adv Ind Sci & Technol, Hlth Res Inst, Kagawa, Japan
关键词
ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE CK2; GENE-EXPRESSION; DNA-BINDING; HYPOXIA; CLOCK; BREAST; PERIOD2;
D O I
10.1371/journal.pone.0109693
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In mammals, the circadian rhythm central generator consists of interactions among clock genes, including Per1/2/3, Cry1/2, Bmal1, and Clock. Circadian rhythm disruption may lead to increased risk of cancer in humans, and deregulation of clock genes has been implicated in many types of cancers. Among these genes, Per2 is reported to have tumor suppressor properties, but little is known about the correlation between Per2 and HIF, which is the main target of renal cell carcinoma (RCC) therapy. In this study, the rhythmic expression of the Per2 gene was not detectable in renal cancer cell lines, with the exception of Caki-2 cells. In Caki-2 cells, HIF1 alpha increased the amplitude of Per2 oscillation by directly binding to the HIF-binding site located on the Per2 promoter. These results indicate that HIF1 alpha may enhance the amplitude of the Per2 circadian rhythm.
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页数:10
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