Circadian time-dependent tumor suppressor function of period genes.
The mammalian core clock genes, Periods (Per1 and Per2), have tumor suppressor properties. Decreased expression of Per1 and Per2 has been reported in several types of human cancers. On the other hand, overexpression of Per1 or Per2 inhibits cancer cell growth in culture. The authors have shown that downregulation of Per1 or Per2 enhances cancer growth in vitro. These genes also regulate the amount of cell proliferation-related molecules, many of which are therapeutic targets. In animals, tumors grow with clear circadian organization, and Per1 and Per2 exert their tumor suppressor functions in a circadian time-dependent manner. Downregulation of Per1 or Per2 increases tumor growth only at certain specific times of the day. Per1 and Per2 differentially regulate tumor growth rhythm in vivo. These data suggest that the therapeutic efficacy of antiproliferation agents depends on the time of day of drug delivery. The optimal times of day may be shifted in tumors that have mutant Period genes.
Yang
Xiaoming
X
Medical Chronobiology Laboratory, WJB Dorn VA Medical Center, Columbia, SC, USA. Xiaoming.yang@va.gov
Wood
Patricia A
PA
Ansell
Christine
C
Hrushesky
William J M
WJ
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D056950:Period Circadian Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D017440:Photoperiod
C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins