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Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis

Antoch, Marina P ; Toshkov, Ilia ; Kuropatwinski, Karen K ; Jackson, Marilyn

Cell cycle (Georgetown, Tex.), 2013-12, Vol.12 (23), p.3673-3680 [Periódico revisado por pares]

United States: Taylor & Francis

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Título:
Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis
Autor: Antoch, Marina P ; Toshkov, Ilia ; Kuropatwinski, Karen K ; Jackson, Marilyn
Assuntos: Aging ; Alleles ; Animals ; Blood Cells - cytology ; Blood Cells - pathology ; Body Weight - radiation effects ; Carcinogenesis - genetics ; Carcinogenesis - radiation effects ; circadian ; Female ; ionizing radiation ; Longevity - radiation effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms - pathology ; PER ; Period Circadian Proteins - deficiency ; Period Circadian Proteins - genetics ; Period Circadian Proteins - metabolism ; Radiation, Ionizing ; sex-specific differences ; tumor suppressor ; tumorigenesis
É parte de: Cell cycle (Georgetown, Tex.), 2013-12, Vol.12 (23), p.3673-3680
Descrição: There is a growing body of evidence that components of the circadian clock are involved in modulation of numerous signaling pathways, and that clock deregulation due to environmental or genetic factors contributes to the development of various pathologies, including cancer. Previous work performed in tissue culture and in in vivo mouse models defined mammalian PERIOD proteins as tumor suppressors, although some experimental inconsistencies (the use of mice on mixed genetic background, lack of sexual discrimination) did not allow a definitive conclusion. To address this issue in a systematic way, we performed a detailed analysis comparing the incidence of tumor development after low-dose ionizing radiation in male and female wild-type, Per1 −/− , and Per2 −/− mice. We showed that in contrast to previous reports deficiency in either Per1 or Per2 genes by itself does not make mice more tumor-prone; moreover, some of the long-term effects of ionizing radiation in Per2-deficient mice are reminiscent more of accelerated aging rather than tumor-prone phenotype. Our histopathological analysis also revealed significant sexual dimorphism both in the rate of radiation-induced tumorigenesis and in the spectrum of tumors developed, which underscores the importance of using sex-matched experimental groups for in vivo studies. Based on our results, we suggest that the role of PER proteins as bona fide tumor suppressors needs to be reevaluated.
Editor: United States: Taylor & Francis
Idioma: Inglês

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Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis

Antoch, Marina P ; Toshkov, Ilia ; Kuropatwinski, Karen K ; Jackson, Marilyn

United States: Taylor & Francis

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