Reference SummaryAntoch MP, Cell Cycle 2013 Dec 1;12(23):3673-80
Title |
Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis. | ||||||
Authors |
Antoch MP; Toshkov I; Kuropatwinski KK; Jackson M | ||||||
Journal |
Cell Cycle | ||||||
Volume |
12 | ||||||
Issue |
23 | ||||||
Year |
2013 | ||||||
Pages |
3673-80 | ||||||
Abstract |
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. | ||||||
Links |
J:223430 – MGI References 24091726 – National Library of Medicine/PubMed |
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Strain Notes
|
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6J | Blood vessel hemangiosarcoma | Blood vessel |
0 |
||
C57BL/6J | Blood vessel hemangiosarcoma |
|
Blood vessel |
0 |
|
B6.129S4-Per1tm1Drw | Blood vessel hemangiosarcoma | Blood vessel |
0 |
||
B6.129S4-Per1tm1Drw | Blood vessel hemangiosarcoma |
|
Blood vessel |
0 |
|
B6.129S4-Per1tm1Drw | Blood vessel hemangiosarcoma |
|
Spleen |
6.25 |
|
B6.129S4-Per2tm1Drw | Blood vessel hemangiosarcoma | Blood vessel |
0 |
||
B6.129S4-Per2tm1Drw | Blood vessel hemangiosarcoma |
|
Blood vessel |
0 |
|
C57BL/6J | Leukocyte leukemia | Leukocyte |
0 |
||
C57BL/6J | Leukocyte leukemia |
|
Leukocyte |
0 |
|
B6.129S4-Per1tm1Drw | Leukocyte leukemia | Leukocyte |
0 |
||
B6.129S4-Per1tm1Drw | Leukocyte leukemia |
|
Leukocyte |
0 - 7.7 |
|
B6.129S4-Per2tm1Drw | Leukocyte leukemia | Leukocyte |
0 |
||
B6.129S4-Per2tm1Drw | Leukocyte leukemia |
|
Leukocyte |
0 |
|
C57BL/6J | Leukocyte lymphoma | Leukocyte |
0 |
||
C57BL/6J | Leukocyte lymphoma |
|
Leukocyte |
5.3 - 21 |
|
B6.129S4-Per1tm1Drw | Leukocyte lymphoma | Leukocyte |
0 - 12.5 |
||
B6.129S4-Per1tm1Drw | Leukocyte lymphoma |
|
Leukocyte |
0 - 15 |
|
B6.129S4-Per1tm1Drw | Leukocyte lymphoma |
|
Thymus |
observed |
|
B6.129S4-Per2tm1Drw | Leukocyte lymphoma | Leukocyte |
0 - 6.7 |
||
B6.129S4-Per2tm1Drw | Leukocyte lymphoma |
|
Leukocyte |
0 - 8.3 |
|
C57BL/6J | Leukocyte lymphoma - lymphosarcoma | Leukocyte |
0 |
||
C57BL/6J | Leukocyte lymphoma - lymphosarcoma |
|
Leukocyte |
0 - 5.3 |
|
B6.129S4-Per1tm1Drw | Leukocyte lymphoma - lymphosarcoma | Leukocyte |
0 - 12.5 |
||
B6.129S4-Per1tm1Drw | Leukocyte lymphoma - lymphosarcoma |
|
Leukocyte |
0 - 6.25 |
|
B6.129S4-Per2tm1Drw | Leukocyte lymphoma - lymphosarcoma | Leukocyte |
0 |
||
B6.129S4-Per2tm1Drw | Leukocyte lymphoma - lymphosarcoma |
|
Leukocyte |
0 |
|
B6.129S4-Per2tm1Drw | Liver - Bile duct cystadenoma |
|
Liver - Bile duct |
7.7 |
|
C57BL/6J | Liver cystadenoma | Liver |
0 |
||
C57BL/6J | Liver cystadenoma |
|
Liver |
0 - 14 |
|
B6.129S4-Per1tm1Drw | Liver cystadenoma | Liver |
0 |
||
B6.129S4-Per1tm1Drw | Liver cystadenoma |
|
Liver |
0 |
|
B6.129S4-Per2tm1Drw | Liver cystadenoma | Liver |
0 |
||
B6.129S4-Per2tm1Drw | Liver cystadenoma |
|
Liver |
8.3 |
|
B6.129S4-Per2tm1Drw | Liver hepatoma |
|
Liver |
observed |
|
C57BL/6J | Ovary - Granulosa cell tumor | Ovary - Granulosa cell |
0 |
||
C57BL/6J | Ovary - Granulosa cell tumor |
|
Ovary - Granulosa cell |
5.3 |
|
B6.129S4-Per1tm1Drw | Ovary - Granulosa cell tumor | Ovary - Granulosa cell |
0 |
||
B6.129S4-Per1tm1Drw | Ovary - Granulosa cell tumor |
|
Ovary - Granulosa cell |
37.5 |
|
B6.129S4-Per2tm1Drw | Ovary - Granulosa cell tumor | Ovary - Granulosa cell |
0 |
||
B6.129S4-Per2tm1Drw | Ovary - Granulosa cell tumor |
|
Ovary - Granulosa cell |
15 |
|
C57BL/6J | Ovary cystadenoma | Ovary |
0 |
||
C57BL/6J | Ovary cystadenoma |
|
Ovary |
42 |
|
B6.129S4-Per1tm1Drw | Ovary cystadenoma | Ovary |
0 |
||
B6.129S4-Per1tm1Drw | Ovary cystadenoma |
|
Ovary |
25 |
|
B6.129S4-Per2tm1Drw | Ovary cystadenoma | Ovary |
0 |
||
B6.129S4-Per2tm1Drw | Ovary cystadenoma |
|
Ovary |
0 |
|
C57BL/6J | Ovary tumor | Ovary |
0 |
||
C57BL/6J | Ovary tumor |
|
Ovary |
47 |
|
B6.129S4-Per1tm1Drw | Ovary tumor | Ovary |
0 |
||
B6.129S4-Per1tm1Drw | Ovary tumor |
|
Ovary |
62.5 |
|
B6.129S4-Per2tm1Drw | Ovary tumor | Ovary |
0 |
||
B6.129S4-Per2tm1Drw | Ovary tumor |
|
Ovary |
15 |
|
C57BL/6J | (Unspecified organ) tumor | (Unspecified organ) |
0 |
||
C57BL/6J | (Unspecified organ) tumor |
|
(Unspecified organ) |
36 - 58 |
|
B6.129S4-Per1tm1Drw | (Unspecified organ) tumor | (Unspecified organ) |
0 - 25 |
||
B6.129S4-Per1tm1Drw | (Unspecified organ) tumor |
|
(Unspecified organ) |
23 - 62.5 |
|
B6.129S4-Per2tm1Drw | (Unspecified organ) tumor | (Unspecified organ) |
0 - 6.7 |
||
B6.129S4-Per2tm1Drw | (Unspecified organ) tumor |
|
(Unspecified organ) |
17 - 23 |