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  • Molecular and Cellular Pathology
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Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo

British Journal of Cancer volume 86, pages 98–101 (2002)Cite this article

Abstract

Hepatocellular carcinoma is a well-known malignancy in the world. However, the molecular mechanism of carcinogenesis and tumour progression remains unclear. Recently, reduced E-cadherin expression due to transcriptional suppressor Snail was proven in a panel of epithelial and dedifferentiated cells derived from carcinomas of various etiologies. In the present study, we examined Snail and E-cadherin mRNA/protein expression in five hepatocellular carcinoma cell lines with variable phenotypes (HuL-1, Hep-G2, Changliver, HLE, and HLF). The results demonstrated that the presence of Snail mRNA in HuL-1, Changliver, HLE and HLF cells detected by RT–PCR, which was further proven by in situ hybridization in tumours induced by HuL-1, Changliver, and HLF cells where Snail mRNA signals expressed in each of the sections. By contrast, E-cadherin mRNA and protein expression were only detected in Hep-G2 cells by RT–PCR and Western blot, respectively. These results were also consistent with the data obtained from in vivo immunohistochemical staining where membranous expression of endogenous E-cadherin protein was revealed only in tumour sections induced by Hep-G2 cells. Here we are the first to report that there is an inverse correlation between Snail and E-cadherin expression in HCC cells as well.

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References

  • Ariizumi SI, Takasaki K, Yamamoto M, Otsubo T, Katagiri S, Saito A (2001) Eight multicentric hepatocellular carcinomas occurring in the same segment of the liver. J Hepatobiliary Pancreat Surg 8: 383–386

    Article  Google Scholar 

  • Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcie De Herreros A (2000) The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2: 84–89

    Article  CAS  Google Scholar 

  • Bergsland EK, Venook AP (2000) Hepatocellular carcinoma. Curr Opin Oncol 12: 357–361

    Article  CAS  Google Scholar 

  • Bracke ME, Van Roy FM, Mareel MM (1996) The E-cadherin/catenin complex in invasion and metastasis. Curr Top Microbiol Immunol 213: 123–161

    CAS  PubMed  Google Scholar 

  • Buendia M (2000) Genetics of hepatocellular carcinoma. Semin Cancer Biol 10: 185–200

    Article  CAS  Google Scholar 

  • Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA (2000) The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2: 76–83

    Article  CAS  Google Scholar 

  • Chang RS (1978) HeLa marker chromosomes, Chang liver cells, and liver-specific functions. Science 199: 567–568

    Article  CAS  Google Scholar 

  • Cook PR (1999) The organization of replication and transcription. Science 284: 1790–1795

    Article  CAS  Google Scholar 

  • Dor I, Namba M, Sato J (1975) Establishment and some biological characteristics of human hepatoma cell lines. Gann 66: 385–392

    CAS  PubMed  Google Scholar 

  • Durr R, Caselmann WH (2000) Carcinogenesis of primary liver malignancies. Langenbecks Arch Surg 385: 154–161

    Article  CAS  Google Scholar 

  • Endo K, Ueda T, Ueyama J, Ohta T, Terada T (2000) Immunoreactive E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin proteins in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, and patients' survival. Hum Pathol 31: 558–565

    Article  CAS  Google Scholar 

  • Feitelson MA (1998) Hepatitis B x antigen and p53 in the development of hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 5: 367–374

    Article  CAS  Google Scholar 

  • Giroldi LA, Bringuier PP, de Weijert M, Jansen C, van Bokhoven A, Schalken JA (1997) Role of E boxes in the repression of E-cadherin expression. Biochem Biophys Res Commun 241: 453–458

    Article  CAS  Google Scholar 

  • Guyton KZ, Kensler TW (1997) Prevention of liver cancer. Curr Opin Oncol 9: 492–496

    Article  CAS  Google Scholar 

  • Hayashi Y, Wang W, Ninomiya T, Nagano H, Ohta K, Itoh H (1999) Liver enriched transcription factors and differentiation of hepatocellular carcinoma. Mol Pathol 52: 19–24

    Article  CAS  Google Scholar 

  • Hedin KE, Kaczynski JA, Gibson MR, Urrutia R (2000) Transcription factors in cell biology, surgery, and transplantation. Surgery 128: 1–5

    Article  CAS  Google Scholar 

  • Hemavathy K, Ashraf SI, Ip YT (2000) Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene 257: 1–12

    Article  CAS  Google Scholar 

  • Hennig G, Lowrick O, Birchmeier W, Behrens J (1996) Mechanisms identified in the transcriptional control of epithelial gene expression. J Biol Chem 271: 595–602

    Article  CAS  Google Scholar 

  • Huang GT, Lee HS, Chen CH, Sheu JC, Chiou LL, Chen DS (1999) Correlation of E-cadherin expression and recurrence of hepatocellular carcinoma. Hepatogastroenterology 46: 1923–1927

    CAS  PubMed  Google Scholar 

  • Huh N, Utakoji T (1981) Production of HBs-antigen by two new human hepatoma cell lines and its enhancement by dexamethasone. Gann 72: 178–179

    CAS  PubMed  Google Scholar 

  • Hussain SP, Harris CC (2000) Molecular epidemiology and carcinogenesis: endogenous and exogenous carcinogens. Mutat Res 462: 311–322

    Article  CAS  Google Scholar 

  • Jiao W, Miyazaki K, Kitajima Y (2001) Exogenous expression of E-cadherin in gallbladder carcinoma cell line G-415 restores its cellular polarity and differentiation. Int J Oncol 19: 1099–1107.

    CAS  PubMed  Google Scholar 

  • Kanai Y, Ushijima S, Hui AM, Ochiai A, Tsuda H, Sakamoto M, Hirohashi S (1997) The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas. Int J Cancer 71: 355–359

    Article  CAS  Google Scholar 

  • Knowles BB, Howe CC, Aden DP (1980) Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209: 497–499

    Article  CAS  Google Scholar 

  • Kojiro M (2000) Premalignant lesions of hepatocellular carcinoma: pathologic viewpoint. J Hepatobiliary Pancreat Surg 5: 367–374

    Google Scholar 

  • Kondoh N, Wakatsuki T, Hada A, Shuda M, Tanaka K, Arai M, Yamamoto M (2001) Genetic and epigenetic events in human hepatocarcinogenesis. Int J Oncol 18: 1271–1278

    CAS  PubMed  Google Scholar 

  • Li LC, Chui RM, Sasaki M, Nakajima K, Perinchery G, Au HC, Nojima D, Carroll P, Dahiya P (2000) A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities. Cancer Res 60: 873–876

    CAS  PubMed  Google Scholar 

  • Oda T (1999) Viral hepatitis and hepatocellular carcinoma prevention strategy in Japan. Jpn J Cancer Res 90: 1051–1060

    Article  CAS  Google Scholar 

  • Okuda K (2000) Hepatocellular carcinoma. J Hepatol 32: 225–237

    Article  CAS  Google Scholar 

  • Osada T, Sakamoto M, Ino Y, Iwamatsu A, Matsuno Y, Muto T, Hirohashi S (1996) E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma. Hepatology 24: 1460–1467

    Article  CAS  Google Scholar 

  • Takeichi M (1991) Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251: 1451–1455

    Article  CAS  Google Scholar 

  • Takeichi M (1993) Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol 5: 806–811

    Article  CAS  Google Scholar 

  • Yokoyama K, Kamata N, Hayashi E, Hoteiya T, Ueda N, Fujimoto R, Nagayama M (2001) Reverse correlation of E-cadherin and snail expression in oral squamous cell carcinoma cells in vitro. Oral Oncol 37: 65–71

    Article  CAS  Google Scholar 

  • Yu MC, Yuan JM, Govindarajan S, Ross RK (2000) Epidemiology of hepatocellular carcinoma. Can J Gastroenterol 14: 703–709

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge Dr Yongxin Chen for histopathological judgement and photography, and Miss Yuko Ichimaru for helping histologic sections.

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  1. Department of Surgery, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    W Jiao, K Miyazaki & Y Kitajima

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  1. W Jiao
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  2. K Miyazaki
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  3. Y Kitajima
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Correspondence to K Miyazaki.

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Jiao, W., Miyazaki, K. & Kitajima, Y. Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo. Br J Cancer 86, 98–101 (2002). https://doi.org/10.1038/sj.bjc.6600017

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  • DOI: https://doi.org/10.1038/sj.bjc.6600017

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