DOI QR코드

DOI QR Code

Clinical Significance of Axin and β-catenin Protein Expression in Primary Hepatocellular Carcinomas

  • Guan, Cheng-Nong (Department of Oncology, the Affiliated Hospital of Guangdong Medical College) ;
  • Chen, Xin-Ming (Department of Oncology, the Affiliated Hospital of Guangdong Medical College) ;
  • Lou, Hai-Qing (Department of Oncology, the Affiliated Hospital of Guangdong Medical College) ;
  • Liao, Xiang-Hui (Department of Oncology, the Affiliated Hospital of Guangdong Medical College) ;
  • Chen, Bao-Ying (Department of Oncology, the Affiliated Hospital of Guangdong Medical College) ;
  • Zhang, Pei-Weng (Department of Oncology, the Affiliated Hospital of Guangdong Medical College)
  • Published : 2012.02.29

Abstract

The aim of the present research was to investigate clinicopathologic correlations of immunohistochemically-demonstrated axin (axis inhibition) and ${\beta}$-catenin expression in primary hepatocellular carcinomas (HCCs), in comparison with paraneoplastic, cirrhotic and normal liver tissues. Variation in Axin expression across groups were significant (P < 0.01), correlating with alpha fetoprotein (AFP), HBsAg, cancer plugs in the portal vein, and clinical stage of HCCs(P < 0.05); however, there were no links with sex, age, and tumour size (P > 0.05). Differences in cell membrane ${\beta}$-catenin expression were also statistically significant (P < 0.01), again correlated with AFP, HBsAg, cancer plugs in the portal vein, and clinical stage in HCCs (P < 0.05) but not with sex, age, and tumour size (P > 0.05). Axin expression levels in tissues with reduced membrane ${\beta}$-catenin were low (P < 0.05), also being low with nuclear ${\beta}$-catenin expression (P < 0.05). Axin and ${\beta}$-catenin may play an important role in the genesis and progression of HCC via the Wnt signal transmission pathway. Simultaneous determination of axin, ${\beta}$-catenin, AFP, and HBsAg may be useful for early diagnosis, and metastatic and clinical staging of HCCs.

Keywords

References

  1. Ashibara K, Saito T, Mizumoto H, et al (2002). Mutation of beta-catenin gene in endometrialcancer but not in associated hyperplasis. Med Electron Microsc, 35, 9-15. https://doi.org/10.1007/s007950200001
  2. Daa T, Kashima K, Kaku N, et al (2004). Mutations in components of the Wnt signaling pathway in adenoid cystic carcinoma. Mod Pathol, 17, 1475-82. https://doi.org/10.1038/modpathol.3800209
  3. Hasegawa T, Yokoyama R, Matsuno Y, et al (2001). Prognostic significance of histologic grade and nuclear expression of beta-catenin in synovial sarcoma. Hum Pathol, 32, 257-63. https://doi.org/10.1053/hupa.2001.22764
  4. Hino S, Michiue T, Asashima M, et al (2003). Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin. J Biol Chem, 278, 14066-73. https://doi.org/10.1074/jbc.M213265200
  5. Jin L H, Shao QJ, Luo W, et al (2003). Detection of point mutations of the Axin1 gene in colorectal cancers. Int J Cancer, 107, 696-9. https://doi.org/10.1002/ijc.11435
  6. Karim R, Tse G, Putti T, et al (2004). The significance of the Wnt pathway in the patho-logy of human cancers. Pathology, 369, 120-8.
  7. Kikuchi A (1999). Roles of Axin in the Wnt signalling pathway. Cell Signal, 11, 777-88. https://doi.org/10.1016/S0898-6568(99)00054-6
  8. Liu C, Li Y, Semenov M, et al (2002). Control of beta-catenin phosphorylation/degradation by a Dual-kinase mechanism. Cell, 108, 837-47. https://doi.org/10.1016/S0092-8674(02)00685-2
  9. Luo W, Lin SC (2004). Axin: a master scaffold for multiple signaling pathways. Neurosignals, 13, 99-113. https://doi.org/10.1159/000076563
  10. Nakajima M, Fukuchi M, Miyazaki T, et al (2003). Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma. Br J Cancer, 88, 1734-9. https://doi.org/10.1038/sj.bjc.6600941
  11. Neo SY, Zhang Y, Yaw LP, et al (2000). Axin-induced apoptosis depends on the extent of its JNK activation and its ability to down-regulate beta-catenin leveks. Biochem Biophys Res Commun, 272, 144-50. https://doi.org/10.1006/bbrc.2000.2751
  12. Pirinen RT, Hirvikoski P, Johansson RT, et al (2001). Reduced expression Of $\alpha$-catenin, $\beta$-catenin, and $\gamma$-catenin is associated with high cell proliferative activity and poor differentiation in nonsmall cell lung cancer. J Clin Pathol, 54, 391-5. https://doi.org/10.1136/jcp.54.5.391
  13. Rubinfeld B, Robbins P, EL-Gamil M, et al (1997). Stailization of $\beta$-catenin by genetic defects in melanoma cell line. Science, 275, 1790-2. https://doi.org/10.1126/science.275.5307.1790
  14. Rui Y, Xu Z, Lin S, et al (2004). Axin stimulates p53 functions by activation of HIPK2 kinase through Multimeric complex formation. EMBO J, 23, 4583-94. https://doi.org/10.1038/sj.emboj.7600475
  15. Satoh S, Daigo Y, Furukawa Y, et al (2000). AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet, 24, 245-50. https://doi.org/10.1038/73448
  16. Takahashi M, Tsunoda T, Seiki M, et al (2002). Identification Of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene, 21, 5861-7. https://doi.org/10.1038/sj.onc.1205755
  17. Ueta T, Ikeguchi M, Hirooka Y, et al (2002). Beta-catenin and cyclin D1 expression in human hepatocellular carcinoma. Oncol Rep, 9, 1197-203.
  18. Zeng L, Fagotto F, Zhang T, et al (1997). The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell, 90, 181-92. https://doi.org/10.1016/S0092-8674(00)80324-4
  19. Zeng L, Fagotto F, Zhang T, et al (1997). The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axin formation. Cell, 90, 181-92. https://doi.org/10.1016/S0092-8674(00)80324-4

Cited by

  1. Inhibition of Wnt signaling induces cell apoptosis and suppresses cell proliferation in cholangiocarcinoma cells vol.30, pp.3, 2013, https://doi.org/10.3892/or.2013.2560
  2. MicroRNA-195 acts as a tumor suppressor by directly targeting Wnt3a in HepG2 hepatocellular carcinoma cells vol.10, pp.5, 2014, https://doi.org/10.3892/mmr.2014.2526
  3. Prognostic Significance of Beta-Catenin Expression in Patients with Esophageal Carcinoma: a Meta-analysis vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6103
  4. PKM2 Regulates Hepatocellular Carcinoma Cell Epithelial-mesenchymal Transition and Migration upon EGFR Activation vol.15, pp.5, 2014, https://doi.org/10.7314/APJCP.2014.15.5.1961
  5. Cytoplasmic and/or Nuclear Expression of β-Catenin Correlate with Poor Prognosis and Unfavorable Clinicopathological Factors in Hepatocellular Carcinoma: A Meta-Analysis vol.9, pp.11, 2014, https://doi.org/10.1371/journal.pone.0111885
  6. Serum Biomarkers for Early Detection of Hepatocellular Carcinoma Associated with HCV Infection in Egyptian Patients vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.1281
  7. Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.3536
  8. Effects of hepatitis C virus core protein and nonstructural protein 4B on the Wnt/β-catenin pathway vol.17, pp.1, 2017, https://doi.org/10.1186/s12866-017-1032-4
  9. A Tale of Two Signals: AR and WNT in Development and Tumorigenesis of Prostate and Mammary Gland vol.9, pp.2, 2017, https://doi.org/10.3390/cancers9020014