Establishment of a mice model with liver-specific AMP-activated protein kinase gene knockout_Journal of Biomedical Engineering

Authors：

TANG Xinghong ¹ , KONG Qingbin ² , JIANG Yangfu ² ,  JING Jing ¹

1. Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;
2. Laboratory of Oncogene, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

JING Jing, Email: jj_zcy@vip.163.com

Keywords：

AMP-activated protein kinase; gene knockout; mice model

DOI：

10.7507/1001-5515.201703025

Video：

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Abstract Full text Figures/Tables Video References Cited by

AMP-activated protein kinase (AMPK) is involved in the development and progression of tumors including hepatocellular carcinoma (HCC). However, studies on AMPK and tumorigenesis were largely based on experiments in vitro or tumor xenografts model. Here, we introduce a liver-specific AMPKα1 knockout mice model, which is achieved by Alb-Cre recombinase system. The expression of AMPKα1 in the liver of AMPKα1^-/--Alb-Cre mice is absent. AMPKα1 knockout in the liver does not affect the growth and histological structure of mouse liver. This model provides a favorable tool to the study of the roles of AMPKα1 in liver metabolism or tumorigenesis.

Citation： TANG Xinghong, KONG Qingbin, JIANG Yangfu, JING Jing. Establishment of a mice model with liver-specific AMP-activated protein kinase gene knockout. Journal of Biomedical Engineering, 2017, 34(3): 415-420. doi: 10.7507/1001-5515.201703025 Copy

1.	Zheng Longyi, Yang Wen, Wu Fuquan, et al. Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma. Clin Cancer Res, 2013, 19(19): 5372-5380.
2.	Hardie D G. AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes, 2013, 62(7): 2164-2172.
3.	Merlen G, Gentric G, Celton-Morizur S, et al. AMPKα1 controls hepatocyte proliferation independently of energy balance by regulating cyclin A2 expression. J Hepatol, 2014, 60(1): 152-159.
4.	Schütte K, Schulz C, Malfertheiner P. Nutrition and hepatocellular cancer. Gastrointest Tumors, 2016, 2(4): 188-194.
5.	Mangels N, Awwad K, Wettenmann A, et al. The soluble epoxide hydrolase determines cholesterol homeostasis by regulating AMPK and SREBP activity. Prostaglandins Other Lipid Mediat, 2016, 125: 30-39.
6.	Ata R, Antonescu C N. Integrins and cell metabolism: an intimate relationship impacting cancer. Int J Mol Sci, 2017, 18(1): E189.
7.	Zhang Jing, Yang Zuozhang, Xie Lin, et al. Statins, autophagy and cancer metastasis. Int J Biochem Cell Biol, 2013, 45(3): 745-752.
8.	Liang J, Mills G B. AMPK: a contextual oncogene or tumor suppressor? Cancer Res, 2013, 73(10): 2929-2935.
9.	Baker L G, Lodge J K. Multiple gene deletion in cryptococcus neoformans using the Cre-lox system. Methods Mol Biol, 2012, 845: 85-98.
10.	Hardie D G, Scott J W, Pan Da, et al. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett, 2003, 546(1): 113-120.
11.	Shaw R J, Bardeesy N, Manning B D, et al. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell, 2004, 6(1): 91-99.
12.	Inoki K, Ouyang Hongjiao, Zhu Tianqing, et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell, 2006, 126(5): 955-968.
13.	Faubert B, Boily G, Izreig S, et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab, 2013, 17(1): 113-124.
14.	Liu Lidan, Ulbrich J, Müller J, et al. Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature, 2012, 483(7391): 608-612.
15.	Mo J S, Meng Zhipeng, Kim Y C, et al. Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway. Nat Cell Biol, 2015, 17(4): 500-510.
16.	Wang Wenqi, Xiao Zhendong, Li Xu, et al. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nat Cell Biol, 2015, 17(4): 490-499.
17.	Kato K, Ogura T, Kishimoto A, et al. Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation. Oncogene, 2002, 21(39): 6082-6090.
18.	Park H U, Suy S, Danner M, et al. AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther, 2009, 8(4): 733-741.
19.	Chhipa R R, Wu Yue, Mohler J L, et al. Survival advantage of AMPK activation to androgen-independent prostate cancer cells during energy stress. Cell Signal, 2010, 22(10): 1554-1561.
20.	Ng T L, Leprivier G, Robertson M D, et al. The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis. Cell Death Differ, 2012, 19(3): 501-510.
21.	Ríos M, Foretz M, Viollet B, et al. AMPK activation by oncogenesis is required to maintain cancer cell proliferation in astrocytic tumors. Cancer Res, 2013, 73(8): 2628-2638.
22.	Ros S, Santos C R, Moco S, et al. Functional metabolic screen identifies 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 as an important regulator of prostate cancer cell survival. Cancer Discov, 2012, 2(4): 328-343.
23.	Chhipa R R, Wu Yue, Ip C. AMPK-mediated autophagy is a survival mechanism in androgen-dependent prostate cancer cells subjected to androgen deprivation and hypoxia. Cell Signal, 2011, 23(9): 1466-1472.
24.	Jeon S M, Chandel N S, Hay N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature, 2012, 485(7400): 661-665.
25.	Li Yingying, Wu Chunjing, Chen Shumei, et al. BRAF inhibitor resistance enhances vulnerability to arginine deprivation in melanoma. Oncotarget, 2016, 7(14): 17665-17680.
26.	Nardo G, Favaro E, Curtarello M, et al. Glycolytic phenotype and AMP kinase modify the pathologic response of tumor xenografts to VEGF neutralization. Cancer Res, 2011, 71(12): 4214-4225.
27.	LIU Xiaona, Chhipa R R, Pooya S, et al. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc Natl Acad Sci U S A, 2014, 111(4): E435-E444.
28.	Vincent E E, Coelho P P, Blagih J, et al. Differential effects of AMPK agonists on cell growth and metabolism. Oncogene, 2015, 34(28): 3627-3639.

1. Zheng Longyi, Yang Wen, Wu Fuquan, et al. Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma. Clin Cancer Res, 2013, 19(19): 5372-5380.
2. Hardie D G. AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes, 2013, 62(7): 2164-2172.
3. Merlen G, Gentric G, Celton-Morizur S, et al. AMPKα1 controls hepatocyte proliferation independently of energy balance by regulating cyclin A2 expression. J Hepatol, 2014, 60(1): 152-159.
4. Schütte K, Schulz C, Malfertheiner P. Nutrition and hepatocellular cancer. Gastrointest Tumors, 2016, 2(4): 188-194.
5. Mangels N, Awwad K, Wettenmann A, et al. The soluble epoxide hydrolase determines cholesterol homeostasis by regulating AMPK and SREBP activity. Prostaglandins Other Lipid Mediat, 2016, 125: 30-39.
6. Ata R, Antonescu C N. Integrins and cell metabolism: an intimate relationship impacting cancer. Int J Mol Sci, 2017, 18(1): E189.
7. Zhang Jing, Yang Zuozhang, Xie Lin, et al. Statins, autophagy and cancer metastasis. Int J Biochem Cell Biol, 2013, 45(3): 745-752.
8. Liang J, Mills G B. AMPK: a contextual oncogene or tumor suppressor? Cancer Res, 2013, 73(10): 2929-2935.
9. Baker L G, Lodge J K. Multiple gene deletion in cryptococcus neoformans using the Cre-lox system. Methods Mol Biol, 2012, 845: 85-98.
10. Hardie D G, Scott J W, Pan Da, et al. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett, 2003, 546(1): 113-120.
11. Shaw R J, Bardeesy N, Manning B D, et al. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell, 2004, 6(1): 91-99.
12. Inoki K, Ouyang Hongjiao, Zhu Tianqing, et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell, 2006, 126(5): 955-968.
13. Faubert B, Boily G, Izreig S, et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab, 2013, 17(1): 113-124.
14. Liu Lidan, Ulbrich J, Müller J, et al. Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature, 2012, 483(7391): 608-612.
15. Mo J S, Meng Zhipeng, Kim Y C, et al. Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway. Nat Cell Biol, 2015, 17(4): 500-510.
16. Wang Wenqi, Xiao Zhendong, Li Xu, et al. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nat Cell Biol, 2015, 17(4): 490-499.
17. Kato K, Ogura T, Kishimoto A, et al. Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation. Oncogene, 2002, 21(39): 6082-6090.
18. Park H U, Suy S, Danner M, et al. AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther, 2009, 8(4): 733-741.
19. Chhipa R R, Wu Yue, Mohler J L, et al. Survival advantage of AMPK activation to androgen-independent prostate cancer cells during energy stress. Cell Signal, 2010, 22(10): 1554-1561.
20. Ng T L, Leprivier G, Robertson M D, et al. The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis. Cell Death Differ, 2012, 19(3): 501-510.
21. Ríos M, Foretz M, Viollet B, et al. AMPK activation by oncogenesis is required to maintain cancer cell proliferation in astrocytic tumors. Cancer Res, 2013, 73(8): 2628-2638.
22. Ros S, Santos C R, Moco S, et al. Functional metabolic screen identifies 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 as an important regulator of prostate cancer cell survival. Cancer Discov, 2012, 2(4): 328-343.
23. Chhipa R R, Wu Yue, Ip C. AMPK-mediated autophagy is a survival mechanism in androgen-dependent prostate cancer cells subjected to androgen deprivation and hypoxia. Cell Signal, 2011, 23(9): 1466-1472.
24. Jeon S M, Chandel N S, Hay N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature, 2012, 485(7400): 661-665.
25. Li Yingying, Wu Chunjing, Chen Shumei, et al. BRAF inhibitor resistance enhances vulnerability to arginine deprivation in melanoma. Oncotarget, 2016, 7(14): 17665-17680.
26. Nardo G, Favaro E, Curtarello M, et al. Glycolytic phenotype and AMP kinase modify the pathologic response of tumor xenografts to VEGF neutralization. Cancer Res, 2011, 71(12): 4214-4225.
27. LIU Xiaona, Chhipa R R, Pooya S, et al. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc Natl Acad Sci U S A, 2014, 111(4): E435-E444.
28. Vincent E E, Coelho P P, Blagih J, et al. Differential effects of AMPK agonists on cell growth and metabolism. Oncogene, 2015, 34(28): 3627-3639.

Journal of Biomedical Engineering

Establishment of a mice model with liver-specific AMP-activated protein kinase gene knockout

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