Reference SummaryKettner NM, Cancer Cell 2016 Dec 12;30(6):909-924
Title |
Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis. |
Authors |
Kettner NM; Voicu H; Finegold MJ; Coarfa C; Sreekumar A; Putluri N; Katchy CA; Lee C; Moore DD; Fu L |
Journal |
Cancer Cell |
Volume |
30 |
Issue |
6 |
Year |
2016 |
Pages |
909-924 |
Abstract |
Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways. Ablation of farnesoid X receptor dramatically increases enterohepatic bile acid levels and jet-lag-induced HCC, while loss of constitutive androstane receptor (CAR), a well-known liver tumor promoter that mediates toxic bile acid signaling, inhibits NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction. |
Links |
J:237981 – MGI References 27889186 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| C57BL/6J | Leukocyte - Lymphocyte - B-lymphocyte tumor |
|
Leukocyte - Lymphocyte - B-lymphocyte |
observed |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Leukocyte - Lymphocyte - B-lymphocyte tumor |
|
Leukocyte - Lymphocyte - B-lymphocyte |
observed |
|
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Leukocyte - Lymphocyte - B-lymphocyte tumor |
|
Leukocyte - Lymphocyte - B-lymphocyte |
observed |
|
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Leukocyte - Lymphocyte - B-lymphocyte tumor |
|
Leukocyte - Lymphocyte - B-lymphocyte |
observed |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Leukocyte - Lymphocyte - B-lymphocyte tumor | Leukocyte - Lymphocyte - B-lymphocyte |
observed |
||
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Leukocyte - Lymphocyte - B-lymphocyte tumor | Leukocyte - Lymphocyte - B-lymphocyte |
observed |
||
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Leukocyte - Lymphocyte - B-lymphocyte tumor | Leukocyte - Lymphocyte - B-lymphocyte |
observed |
||
| C57BL/6J | Liver hepatocellular carcinoma | Liver |
0 |
||
| C57BL/6J | Liver hepatocellular carcinoma |
|
Liver |
observed - 8.75 |
|
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Liver hepatocellular carcinoma | Liver |
observed - 11.67 |
||
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Liver hepatocellular carcinoma |
|
Liver |
observed - 17.86 |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Liver hepatocellular carcinoma | Liver |
observed - 12.5 |
||
| B6.129-Per1tm1Brd Per2tm1Ccl | Liver hepatocellular carcinoma |
|
Liver |
observed - 20 |
|
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Liver hepatocellular carcinoma | Liver |
observed - 11.54 |
||
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Liver hepatocellular carcinoma |
|
Liver |
observed - 11.63 |
|
| C57BL/6J-Nr1i3tm1Ddm | Liver hepatocellular carcinoma | Liver |
0 |
||
| C57BL/6J-Nr1i3tm1Ddm | Liver hepatocellular carcinoma |
|
Liver |
0 |
|
| C57BL/6J-Nr1h4tm1Gonz | Liver hepatocellular carcinoma | Liver |
28 |
||
| C57BL/6J-Nr1h4tm1Gonz | Liver hepatocellular carcinoma |
|
Liver |
61.29 |
|
| C57BL/6J | Liver hyperplasia | Liver |
15.45 |
||
| C57BL/6J | Liver hyperplasia |
|
Liver |
75 |
|
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Liver hyperplasia | Liver |
68.33 |
||
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Liver hyperplasia |
|
Liver |
69.64 |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Liver hyperplasia | Liver |
86.25 |
||
| B6.129-Per1tm1Brd Per2tm1Ccl | Liver hyperplasia |
|
Liver |
86 |
|
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Liver hyperplasia | Liver |
73.08 |
||
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Liver hyperplasia |
|
Liver |
95.35 |
|
| C57BL/6J-Nr1i3tm1Ddm | Liver hyperplasia | Liver |
25 |
||
| C57BL/6J-Nr1i3tm1Ddm | Liver hyperplasia |
|
Liver |
0 |
|
| C57BL/6J-Nr1h4tm1Gonz | Liver hyperplasia | Liver |
100 |
||
| C57BL/6J-Nr1h4tm1Gonz | Liver hyperplasia |
|
Liver |
100 |
|
| C57BL/6J | Ovary tumor |
|
Ovary |
observed |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Ovary tumor |
|
Ovary |
observed |
|
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Ovary tumor |
|
Ovary |
observed |
|
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Ovary tumor |
|
Ovary |
observed |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Ovary tumor | Ovary |
observed |
||
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Ovary tumor | Ovary |
observed |
||
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Ovary tumor | Ovary |
observed |
||
| C57BL/6J | Pancreas tumor |
|
Pancreas |
observed |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Pancreas tumor |
|
Pancreas |
observed |
|
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Pancreas tumor |
|
Pancreas |
observed |
|
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Pancreas tumor |
|
Pancreas |
observed |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | Pancreas tumor | Pancreas |
observed |
||
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | Pancreas tumor | Pancreas |
observed |
||
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | Pancreas tumor | Pancreas |
observed |
||
| C57BL/6J | (Unspecified organ) tumor | (Unspecified organ) |
0 |
||
| C57BL/6J | (Unspecified organ) tumor |
|
(Unspecified organ) |
observed |
|
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | (Unspecified organ) tumor | (Unspecified organ) |
observed |
||
| B6.129P2-Cry1tm1Asn Cry2tm1Asn | (Unspecified organ) tumor |
|
(Unspecified organ) |
observed |
|
| B6.129-Per1tm1Brd Per2tm1Ccl | (Unspecified organ) tumor | (Unspecified organ) |
observed |
||
| B6.129-Per1tm1Brd Per2tm1Ccl | (Unspecified organ) tumor |
|
(Unspecified organ) |
observed |
|
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | (Unspecified organ) tumor | (Unspecified organ) |
observed |
||
| B6.Cg-Bmal1tm1Weit Speer6-ps1Tg(Alb-cre)21Mgn/? | (Unspecified organ) tumor |
|
(Unspecified organ) |
observed |