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A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury

  • Authors:
    • Hye Shin Lee
    • Jinhyeok Choi
    • Taekwon Son
    • Eun Ji Lee
    • Jeong‑Gyun Kim
    • Soo Hyung Ryu
    • Danbi Lee
    • Myoung Kuk Jang
    • Eunsil Yu
    • Young‑Hwa Chung
    • Irwin H. Gelman
    • Kyu‑Won Kim
  • View Affiliations / Copyright

    Affiliations: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea, Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul 04551, Republic of Korea, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea, Department of Internal Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul 05355, Republic of Korea, Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea, Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5907-5915
    |
    Published online on: September 4, 2018
       https://doi.org/10.3892/ol.2018.9396
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Abstract

AKAP12 belongs to A‑kinase anchoring protein (AKAP) family of scaffold proteins and is known as a tumor suppressor in several human cancer types. Its role as a tumor suppressor in hepatocellular carcinoma (HCC) was proposed due to its downregulation and epigenetic modification in human HCC; however, the effect of its deficiency on liver injuries, such as liver fibrosis and cancer has been poorly studied. By analyzing tumor and non‑tumor tissues of 15 patients with HCC, it was confirmed that AKAP12 expression was downregulated in human HCC as compared with adjacent non‑tumor tissues. Immunohistochemical staining of mouse liver tissue for AKAP12 revealed that its sinusoidal expression was diminished in capillarized endothelium after 8 weeks of thioacetamide (TAA) administration. AKAP12 deficiency resulted in the promotion of ductular response of biliary epithelial cells, whereas overall fibrosis and myofibroblast activation were comparable between genotypes after short‑term TAA treatment. The mRNA expressions of some fibrosis‑related genes such as those encoding epithelial cell adhesion molecule, collagen type 1 α1 and elastin were upregulated in liver tissues of AKAP12‑knockout mice. Long‑term administration of TAA for 26 weeks led to the development of liver tumors; the incidence of tumor development was higher in AKAP12‑deficient mice than in wild‑type littermates. Together, these results suggest that AKAP12 functions as a tumor suppressor in liver cancer and is associated with the regulation of hepatic non‑parenchymal cells.
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Copy and paste a formatted citation
Spandidos Publications style
Lee HS, Choi J, Son T, Lee EJ, Kim JG, Ryu SH, Lee D, Jang MK, Yu E, Chung YH, Chung YH, et al: A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury. Oncol Lett 16: 5907-5915, 2018.
APA
Lee, H.S., Choi, J., Son, T., Lee, E.J., Kim, J., Ryu, S.H. ... Kim, K. (2018). A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury. Oncology Letters, 16, 5907-5915. https://doi.org/10.3892/ol.2018.9396
MLA
Lee, H. S., Choi, J., Son, T., Lee, E. J., Kim, J., Ryu, S. H., Lee, D., Jang, M. K., Yu, E., Chung, Y., Gelman, I. H., Kim, K."A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury". Oncology Letters 16.5 (2018): 5907-5915.
Chicago
Lee, H. S., Choi, J., Son, T., Lee, E. J., Kim, J., Ryu, S. H., Lee, D., Jang, M. K., Yu, E., Chung, Y., Gelman, I. H., Kim, K."A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury". Oncology Letters 16, no. 5 (2018): 5907-5915. https://doi.org/10.3892/ol.2018.9396
Copy and paste a formatted citation
x
Spandidos Publications style
Lee HS, Choi J, Son T, Lee EJ, Kim JG, Ryu SH, Lee D, Jang MK, Yu E, Chung YH, Chung YH, et al: A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury. Oncol Lett 16: 5907-5915, 2018.
APA
Lee, H.S., Choi, J., Son, T., Lee, E.J., Kim, J., Ryu, S.H. ... Kim, K. (2018). A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury. Oncology Letters, 16, 5907-5915. https://doi.org/10.3892/ol.2018.9396
MLA
Lee, H. S., Choi, J., Son, T., Lee, E. J., Kim, J., Ryu, S. H., Lee, D., Jang, M. K., Yu, E., Chung, Y., Gelman, I. H., Kim, K."A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury". Oncology Letters 16.5 (2018): 5907-5915.
Chicago
Lee, H. S., Choi, J., Son, T., Lee, E. J., Kim, J., Ryu, S. H., Lee, D., Jang, M. K., Yu, E., Chung, Y., Gelman, I. H., Kim, K."A‑kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide‑induced liver injury". Oncology Letters 16, no. 5 (2018): 5907-5915. https://doi.org/10.3892/ol.2018.9396
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