共 20 条
Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor
被引:390
作者:

Yang, Fan
论文数: 0 引用数: 0
h-index: 0
机构: City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA

Huang, Xiongfei
论文数: 0 引用数: 0
h-index: 0
机构: City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA

Yi, Tangsheng
论文数: 0 引用数: 0
h-index: 0
机构: City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA

Yen, Yun
论文数: 0 引用数: 0
h-index: 0
机构: City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA

Moore, David D.
论文数: 0 引用数: 0
h-index: 0
机构: City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA

Huang, Wendong
论文数: 0 引用数: 0
h-index: 0
机构: City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA
机构:
[1] City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA
[2] City Hope Natl Med Ctr, Beckman Res Inst, Dept Clin & Mol Pharmacol, Duarte, CA 91010 USA
[3] Fujian Med Univ, Fujian, Peoples R China
[4] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词:
D O I:
10.1158/0008-5472.CAN-06-1078
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear hormone receptor superfamily, which plays an essential role in regulating bile acid, lipid, and glucose homeostasis. Both male and female FXR-/- mice spontaneously developed liver tumors; however, no other tumors were developed after 15 months of age. In contrast, no liver tumors were observed in wild-type mice of the same age. Histologic analyses confirm that tumors were hepatocellular adenoma and carcinoma. Although there was no obvious tumor at ages 9 to 12 months, FXR-/- livers displayed prominent liver injury and inflammation. Strong labeling of apoptotic hepatocytes and liver damage-induced compensatory regeneration were observed. Deregulation of genes involved in bile acid homeostasis in FXR-/- mice was consistent with abnormal levels of bile acids presented in serum and liver. Genes involved in inflammation and cell cycle were up-regulated in aging FXR-/- mice but not in wild-type controls. Increasing the bile acid levels by feeding mice with a 0.2% cholic acid diet strongly promoted N-nitrosodiethylamine-initiated liver tumorigenesis, whereas lowering bile acid pool in FXR-/- mice by a 2% cholestyramine feeding significantly reduced the malignant lesions. Our results suggest an intriguing link between metabolic regulation and hepatocarcinogenesis.
引用
收藏
页码:863 / 867
页数:5
相关论文
共 20 条
[1]
Cancer - An inflammatory link
[J].
Balkwill, F
;
Coussens, LM
.
NATURE,
2004, 431 (7007)
:405-406

Balkwill, F
论文数: 0 引用数: 0
h-index: 0
机构: Barts & London Queen Marys Med Sch, Canc Res UK Translat Oncol Lab, London EC1M 6BQ, England

Coussens, LM
论文数: 0 引用数: 0
h-index: 0
机构: Barts & London Queen Marys Med Sch, Canc Res UK Translat Oncol Lab, London EC1M 6BQ, England
[2]
Influence of ursodeoxycholate-enriched diet on liver tumor growth in HBV transgenic mice
[J].
Barone, M
;
Maiorano, E
;
Ladisa, R
;
Cuomo, R
;
Pece, A
;
Berloco, P
;
Caruso, ML
;
Valentini, AM
;
Iolascon, A
;
Francavilla, A
;
Di Leo, A
;
Ierardi, E
.
HEPATOLOGY,
2003, 37 (04)
:880-886

Barone, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Maiorano, E
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Ladisa, R
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Cuomo, R
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Pece, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Berloco, P
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Caruso, ML
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Valentini, AM
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Iolascon, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Francavilla, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Di Leo, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy

Ierardi, E
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bari, Cattedra Gastroenterol, Policlin, Sect Gastroenterol,Dept Emergency & Organ Transpl, I-70124 Bari, Italy
[3]
The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice
[J].
Cariou, B
;
van Harmelen, K
;
Duran-Sandoval, D
;
van Dijk, TH
;
Grefhorst, A
;
Abdelkarim, M
;
Caron, S
;
Torpier, G
;
Fruchart, JC
;
Gonzalez, FJ
;
Kuipers, F
;
Staels, B
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2006, 281 (16)
:11039-11049

Cariou, B
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

van Harmelen, K
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Duran-Sandoval, D
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

van Dijk, TH
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Grefhorst, A
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Abdelkarim, M
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Caron, S
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Torpier, G
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Fruchart, JC
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Gonzalez, FJ
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Kuipers, F
论文数: 0 引用数: 0
h-index: 0
机构: Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

Staels, B
论文数: 0 引用数: 0
h-index: 0
机构:
Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France
[4]
A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
[J].
Goodwin, B
;
Jones, SA
;
Price, RR
;
Watson, MA
;
McKee, DD
;
Moore, LB
;
Galardi, C
;
Wilson, JG
;
Lewis, MC
;
Roth, ME
;
Maloney, PR
;
Willson, TM
;
Kliewer, SA
.
MOLECULAR CELL,
2000, 6 (03)
:517-526

Goodwin, B
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Jones, SA
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Price, RR
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Watson, MA
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

McKee, DD
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Moore, LB
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Galardi, C
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Wilson, JG
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Lewis, MC
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Roth, ME
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Maloney, PR
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Willson, TM
论文数: 0 引用数: 0
h-index: 0
机构: Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA

Kliewer, SA
论文数: 0 引用数: 0
h-index: 0
机构:
Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA Glaxo Wellcome Res & Dev Ltd, Dept Mol Endocrinol, Res Triangle Pk, NC 27709 USA
[5]
IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer
[J].
Greten, FR
;
Eckmann, L
;
Greten, TF
;
Park, JM
;
Li, ZW
;
Egan, LJ
;
Kagnoff, MF
;
Karin, M
.
CELL,
2004, 118 (03)
:285-296

Greten, FR
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA

Eckmann, L
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA

Greten, TF
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA

Park, JM
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA

Li, ZW
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA

Egan, LJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA

Kagnoff, MF
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA

Karin, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA
[6]
Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration
[J].
Huang, WD
;
Ma, K
;
Zhang, J
;
Qatanani, M
;
Cuvillier, J
;
Liu, J
;
Dong, BN
;
Huang, XF
;
Moore, DD
.
SCIENCE,
2006, 312 (5771)
:233-236

Huang, WD
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Ma, K
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Zhang, J
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Qatanani, M
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Cuvillier, J
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Liu, J
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Dong, BN
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Huang, XF
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

Moore, DD
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[7]
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
[J].
Inagaki, T
;
Moschetta, A
;
Lee, YK
;
Peng, L
;
Zhao, GX
;
Downes, M
;
Yu, RT
;
Shelton, JM
;
Richardson, JA
;
Repa, JJ
;
Mangelsdorf, DJ
;
Kliewer, SA
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2006, 103 (10)
:3920-3925

Inagaki, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Moschetta, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Lee, YK
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Peng, L
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Zhao, GX
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Downes, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Yu, RT
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Shelton, JM
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Richardson, JA
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Repa, JJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Mangelsdorf, DJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

Kliewer, SA
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA
[8]
LXRs AND FXR: The Yin and Yang of cholesterol and fat metabolism
[J].
Kalaany, NY
;
Mangelsdorf, DJ
.
ANNUAL REVIEW OF PHYSIOLOGY,
2006, 68
:159-191

Kalaany, NY
论文数: 0 引用数: 0
h-index: 0
机构:
MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

Mangelsdorf, DJ
论文数: 0 引用数: 0
h-index: 0
机构: MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[9]
The farnesoid X-receptor is an essential regulator of cholesterol homeostasis
[J].
Lambert, G
;
Amar, MJA
;
Guo, G
;
Brewer, HB
;
Gonzalez, FJ
;
Sinal, CJ
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2003, 278 (04)
:2563-2570

Lambert, G
论文数: 0 引用数: 0
h-index: 0
机构: Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada

Amar, MJA
论文数: 0 引用数: 0
h-index: 0
机构: Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada

Guo, G
论文数: 0 引用数: 0
h-index: 0
机构: Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada

Brewer, HB
论文数: 0 引用数: 0
h-index: 0
机构: Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada

Gonzalez, FJ
论文数: 0 引用数: 0
h-index: 0
机构: Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada

Sinal, CJ
论文数: 0 引用数: 0
h-index: 0
机构: Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada
[10]
Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors
[J].
Lu, TT
;
Makishima, M
;
Repa, JJ
;
Schoonjans, K
;
Kerr, TA
;
Auwerx, J
;
Mangelsdorf, DJ
.
MOLECULAR CELL,
2000, 6 (03)
:507-515

Lu, TT
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA

Makishima, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA

Repa, JJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA

Schoonjans, K
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA

Kerr, TA
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA

Auwerx, J
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA

Mangelsdorf, DJ
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA