Skip to main navigation Skip to main content

CMH : Clinical and Molecular Hepatology

OPEN ACCESS
Search
Advanced Search
ABOUT
BROWSE ARTICLES
FOR CONTRIBUTORS

Articles

Page Path

Editorial

P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma

Yu Rim Lee, Soo Young Park
Clinical and Molecular Hepatology 2015;21(3):230-231.
Published online: September 30, 2015

Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.

Corresponding author: Soo Young Park. Department of Internal Medicine, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea. Tel: +82-53-200-5519, Fax: +82-53-426-8773, psyoung0419@gmail.com
• Received: August 7, 2015   • Revised: August 27, 2015

Copyright © 2015 by The Korean Association for the Study of the Liver

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 9,347 Views
  • 78 Download
  • 13 Web of Science
  • 12 Crossref
  • 13 Scopus
prev next

Full Article

Download PDF Download PDF
See the article "Influence of P53 on the radiotherapy response of hepatocellular carcinoma" on page 257.
  • Keywords: Hepatocellular carcinoma; Radiotherapy; P53
    • See Article on Page [Related article:] 257
    Hepatocellular carcinoma (HCC) is the second leading cause of cancer related death with increasing incidence.1 The standard treatments of HCC consist of surgical resection, liver transplantation, radiofrequency ablation and transarterial chemoembolization. However, because a large proportion of HCC patients are diagnosed in advanced stage, long-term prognosis is disappointing with few available therapeutic modalities.23
    Although Radiotherapy is not included in the Barcelona Clinic Liver Cancer (BCLC) algorithm, it has shown acceptable therapeutic efficacy as one of the therapeutic options for HCC patients.4 However, as HCC often acquires radioresistance which are correlated with treatment failure,5 only a small number of radionuclides, such as iodine-131, yttrium-90, rhenium-188 and holmium-166, have been used to the HCC treatment.67 The P53 protein is a transcription factor related to DNA damage repair, growth arrest and apoptosis leading to uncontrolled proliferation, associated with more than 50% of human cancers.8910 P53 normally exists in low steady level, but the expression and activation of P53 increases after radiation. The P53 is thought to be one of the key elements involved in the response to radiotherapy.8 Many studies have been conducted for elucidating relationship between P53 and effectiveness of radiotherapy in cancer and revealed that mutation or inactivation of P53 causes genetic instability, resulting in development of tumors and ineffectiveness of radiotherapy.91011
    In this issue, Gomes et al. reported influence of P53 on the radiotherapeutic response of the HCC. In this study, investigation of the effect of iodine-131 radiotherapy in three human HCC cell lines with different degrees of P53 expression was conducted to assess the influence of P53 on the HCC cell survival after radiation therapy. As a result, Hep3B2.1-7 cell line, which has a homozygous deletion in the TP53 gene, did not express P53, HepG2 expresses its normal form, and HuH7, which has a mutated codon, overexpressed P53. For HepG2 and HuH7 cell lines, an increase in P53 expression was observed after both external and internal radiation with I-131, especially in HuH7. Level of phosphorylated P53 was higher after external irradiation than internal radiation with highest levels of phosphorylation in HepG2 cell line. The Hep3B2.1-7 cells were less radiosensitive than other two cell lines. More radiosensitive cell lines, which exhibit a great decrease in cell survival (HepG2, HbH7) showed a higher expression of P53. Thus, P53 protein, encoded by the TP 53 tumor suppressor gene, might be an important factor in radiotherapeutic response in HCC, which is consistent with previous studies.910
    Although P53 triggered most apoptotic cell death, in this study, cells died by late apoptosis/necrosis and necrosis. We must consider the possibility of the aggressiveness of radiation to cells or observation of cell death in later stage. Moreover, HepG2 cell line is more sensitive to both external and internal radiation than HuH7 cell line. It might be related to the character of HepG2 cell line which expressed the normal and more functional form of P53.
    Further studies are warranted about more detail signaling pathways. It would be an important target for HCC treatment.

    Conflicts of Interest: The authors have no conflicts to disclose.

    BCLC

    Barcelona Clinic Liver Cancer

    HCC

    hepatocellular carcinoma
    • 1. World Health Organization. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalende Worldwide in 2012. WHO web site. Accessed Aug. 5, 2015]. http://globocan.iarc.fr/Default.aspx.
    • 2. Thomas MB, Zhu AX. Hepatocellular carcinoma: the need for progress. J Clin Oncol 2005;23:2892-2899. 15860847.
    • 3. Schwartz JM, Ham JM. Treatment of Hepatocellular Carcinoma. Curr Treat Options Gastroenterol 2003;6:465-472. 14585235.
    • 4. Toya R, Murakami R, Baba Y, Nishimura R, Morishita S, Ikeda O, et al. Conformal radiation therapy for portal vein tumor thrombosis of hepatocellular carcinoma. Radiother Oncol 2007;84:266-271. 17716760.
    • 5. Kim JJ, Tannock IF. Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer 2005;5:516-525. 15965493.
    • 6. Keng GH, Sundram FX. Radionuclide therapy of hepatocellular carcinoma. Ann Acad Med Singapore 2003;32:518-524. 12968558.
    • 7. Raoul JL, Boucher E, Rolland Y, Garin E. Treatment of hepatocellular carcinoma with intra-arterial injection of radionuclides. Nat Rev Gastroenterol Hepatol 2010;7:41-49. 20051971.
    • 8. Gudkov AV, Komarova EA. The role of p53 in determining sensitivity to radiotherapy. Nat Rev Cancer 2003;3:117-129. 12563311.
    • 9. Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 2011;11:239-253. 21430696.
    • 10. Levine AJ, Oren M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer 2009;9:749-758. 19776744.
    • 11. He M, Zhao M, Shen B, Prise KM, Shao C. Radiation-induced intercellular signaling mediated by cytochrome-c via a p53-dependent pathway in hepatoma cells. Oncogene 2011;30:1947-1955. 21132005.

    Download Citation

    Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

    Format:

    Include:

    P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma
    Clin Mol Hepatol. 2015;21(3):230-231.   Published online September 30, 2015
    DOI: https://doi.org/10.3350/cmh.2015.21.3.230
    Download Citation

    Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
    Format:
    Include:
    P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma
    Clin Mol Hepatol. 2015;21(3):230-231.   Published online September 30, 2015
    DOI: https://doi.org/10.3350/cmh.2015.21.3.230
    Close

    Related articles

    P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma
    P53 expression in hepatocellular carcinoma: influence on the radiotherapeutic response of the hepatocellular carcinoma
    CMH : Clinical and Molecular Hepatology
    Twitter

    ABOUT

    BROWSE ARTICLES

    FOR CONTRIBUTORS

    © The Korean Association for the Study of the Liver.