Expression of neighbor of Punc E11 in hepatocarcinogenesis induced by diethylnitrosamine

Kim,Young  Hee; Kwak,Kyung  A; Kang,Jin  Seok

doi:10.3892/or.2014.3285

Expression of neighbor of Punc E11 in hepatocarcinogenesis induced by diethylnitrosamine

Authors:
- Young Hee Kim
- Kyung A Kwak
- Jin Seok Kang
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Affiliations: Department of Biomedical Laboratory Science, Namseoul University, Cheonan 330-707, Republic of Korea
Published online on: June 23, 2014 https://doi.org/10.3892/or.2014.3285
Pages: 1043-1049

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Abstract

To identify preneoplastic markers for hepatocarcinogenesis, the expression levels of neighbor of Punc E11 (Nope), E-cadherin and α-fetoprotein (AFP) were investigated in carcinogen-treated embryonic cell lineages. Mouse embryonic stem cells (ESCs), hepatic progenitor cells (HPCs), and hepatocyte‑like cells (HCs) representing 0, 22, and 40 days of liver differentiation, respectively, were treated in vitro with diethylnitrosamine (DEN) at 4 doses (0, 1, 5, and 15 mM) for 24 h. The expression of Nope, E-cadherin and AFP was examined by quantitative real-time PCR, western blotting and immunocytochemistry. DEN treatment significantly increased the mRNA expression of Nope in ESCs and HPCs, and that of E-cadherin and AFP in all three cell lines, although the changes in expression were triggered by varying DEN concentrations. Immunofluorescence staining revealed that Nope was expressed at the cell membrane in ESCs and HPCs and within granules or in the cytoplasm of HCs, which was also stained by E-cadherin. DEN treatment induced Nope expression in ESCs, HPCs and HCs and caused a concomitant increase in E-cadherin expression. Although Nope expression clearly increased following tumor induction, its expression pattern changed with the developmental stage. In conclusion, we determined that Nope expression may carry prognostic significance during early hepatocarcinogenesis. Moreover, Nope expression may serve as a novel oncofetal surface marker for preneoplastic stages that are not identifiable by the commonly used marker, AFP.

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1	Greenhough S, Medine CN and Hay DC: Pluripotent stem cell derived hepatocyte like cells and their potential in toxicity screening. Toxicology. 278:250–255. 2010. View Article : Google Scholar : PubMed/NCBI
2	Okura H, Komoda H, Saga A, et al: Properties of hepatocyte-like cell clusters from human adipose tissue-derived mesenchymal stem cells. Tissue Engineering Part C Methods. 16:761–770. 2010. View Article : Google Scholar : PubMed/NCBI
3	Hamazaki T, Iiboshi Y, Oka M, et al: Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Lett. 497:15–19. 2001. View Article : Google Scholar : PubMed/NCBI
4	Touboul T, Hannan NR, Corbineau S, et al: Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology. 51:1754–1765. 2010. View Article : Google Scholar
5	Rambhatla L, Chiu C-P, Kundu P, Peng Y and Carpenter MK: Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplant. 12:1–11. 2003. View Article : Google Scholar : PubMed/NCBI
6	Abelev GI, Perova SD, Khramkova NI, Postnikova ZA and Irlin IS: Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation. 1:174–180. 1963. View Article : Google Scholar : PubMed/NCBI
7	Bruix J and Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology. 42:1208–1236. 2005. View Article : Google Scholar
8	Visvader JE and Lindeman GJ: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 2008. View Article : Google Scholar : PubMed/NCBI
9	Schievenbusch S, Schrammel T, Goeser T and Nierhoff D: Neighbor of Punc E11 in the Mdr2^-/- mouse model: Novel marker of stem/progenitor cells in regenerating adult liver. Hepatology. Wiley-Blackwell; MA: pp. 962A. 2011
10	Schievenbusch S, Sauer E, Curth HM, et al: Neighbor of Punc E 11: expression pattern of the new hepatic stem/progenitor cell marker during murine liver development. Stem Cells. 21:2656–2666. 2012. View Article : Google Scholar : PubMed/NCBI
11	Salbaum JM and Kappen C: Cloning and expression of nope, a new mouse gene of the immunoglobulin superfamily related to guidance receptors. Genomics. 64:15–23. 2000. View Article : Google Scholar : PubMed/NCBI
12	Marquardt JU, Quasdorff M, Varnholt H, et al: Neighbor of Punc E11, a novel oncofetal marker for hepatocellular carcinoma. Int J Cancer. 128:2353–2363. 2011. View Article : Google Scholar : PubMed/NCBI
13	He G, Dhar D, Nakagawa H, et al: Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell. 155:384–396. 2013. View Article : Google Scholar : PubMed/NCBI
14	Sato Y, Nakata K, Kato Y, et al: Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med. 328:1802–1806. 1993. View Article : Google Scholar : PubMed/NCBI
15	Sell S and Dunsford H: Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol. 134:13471989.PubMed/NCBI
16	Gebo KA, Chander G, Jenckes MW, et al: Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: a systematic review. Hepatology. 36:S84–S92. 2002. View Article : Google Scholar : PubMed/NCBI
17	Gupta S, Bent S and Kohlwes J: Test characteristics of α-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C: A systematic review and critical analysis. Ann Intern Med. 139:46–50. 2003.
18	Marrero JA and Feng Z: Alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology. 138:400–401. 2010. View Article : Google Scholar : PubMed/NCBI
19	Forner A, Reig M and Bruix J: α-fetoprotein for hepatocellular carcinoma diagnosis: the demise of a brilliant star. Gastroenterology. 137:26–29. 2009.
20	Marrero JA, Feng Z, Wang Y, et al: Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology. 137:110–118. 2009. View Article : Google Scholar : PubMed/NCBI
21	Kubota H and Reid LM: Clonogenic hepatoblasts, common precursors for hepatocytic and biliary lineages, are lacking classical major histocompatibility complex class I antigen. Proc Natl Acad Sci USA. 97:12132–12137. 2000. View Article : Google Scholar
22	Suzuki A, Zheng YW, Kondo R, et al: Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology. 32:1230–1239. 2000. View Article : Google Scholar : PubMed/NCBI
23	Watanabe T, Nakagawa K, Ohata S, et al: SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-kappaB-induced anti-apoptosis. Dev Biol. 250:332–347. 2002. View Article : Google Scholar : PubMed/NCBI
24	Tanimizu N, Nishikawa M, Saito H, Tsujimura T and Miyajima A: Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J Cell Sci. 116:1775–1786. 2003. View Article : Google Scholar : PubMed/NCBI
25	Nierhoff D, Ogawa A, Oertel M, Chen YQ and Shafritz DA: Purification and characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. Hepatology. 42:130–139. 2005. View Article : Google Scholar : PubMed/NCBI
26	Nitou M, Sugiyama Y, Ishikawa K and Shiojiri N: Purification of fetal mouse hepatoblasts by magnetic beads coated with monoclonal anti-e-cadherin antibodies and their in vitro culture. Exp Cell Res. 279:330–343. 2002. View Article : Google Scholar : PubMed/NCBI
27	Rabes H: Development and growth of early preneoplastic lesions induced in the liver by chemical carcinogens. J Cancer Res Clin Oncol. 106:85–92. 1983. View Article : Google Scholar : PubMed/NCBI
28	Kang JS, Kang HG, Park YI, et al: Expression of epithelial cell adhesion molecule and proliferating cell nuclear antigen in diethylnitrosamine induced hepatocarcinogenesis in mice. Exp Ther Med. 5:138–142. 2013.PubMed/NCBI
29	Kang JS: Expression of epithelial cell adhesion molecule in early phase of hepatocarcinogenesis of mice treated with diethylnitrosamine. J Biomed Res. 13:243–247. 2012.
30	Fausto N and Campbell JS: Mouse models of hepatocellular carcinoma. Seminars in Liver Disease. Thieme Medical Publishers; pp. 087–098. 2010, View Article : Google Scholar
31	Kang JS, Wanibuchi H, Morimura K, Gonzalez FJ and Fukushima S: Role of CYP2E1 in diethylnitrosamine-induced hepatocarcinogenesis in vivo. Cancer Res. 67:11141–11146. 2007. View Article : Google Scholar : PubMed/NCBI
32	Bannasch P: Sequential cellular changes during chemical carcinogenesis. J Cancer Res Clin Oncol. 108:11–22. 1984. View Article : Google Scholar : PubMed/NCBI
33	Zhang BH, Yang BH and Tang ZY: Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 130:417–422. 2004. View Article : Google Scholar : PubMed/NCBI
34	Song BC, Chung YH, Kim JA, et al: Transforming growth factor-β1 as a useful serologic marker of small hepatocellular carcinoma. Cancer. 94:175–180. 2002.
35	Li D, Mallory T and Satomura S: AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta. 313:15–19. 2001. View Article : Google Scholar : PubMed/NCBI
36	Marrero JA, Su GL, Wei W, et al: Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients. Hepatology. 37:1114–1121. 2003. View Article : Google Scholar : PubMed/NCBI
37	Capurro M, Wanless IR, Sherman M, et al: Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 125:89–97. 2003. View Article : Google Scholar : PubMed/NCBI
38	Marrero JA, Romano PR, Nikolaeva O, et al: GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol. 43:1007–1012. 2005. View Article : Google Scholar : PubMed/NCBI
39	Morford LA, Davis C, Jin L, Dobierzewska A, Peterson ML and Spear BT: The oncofetal gene glypican 3 is regulated in the postnatal liver by zinc fingers and homeoboxes 2 and in the regenerating liver by alpha-fetoprotein regulator 2. Hepatology. 46:1541–1547. 2007. View Article : Google Scholar : PubMed/NCBI