- Volume 14 Issue 7
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Effects of Parafibromin Expression on the Phenotypes and Relevant Mechanisms in the DLD-1 Colon Carcinoma Cell Line
- Zhao, Shuang (Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University) ;
- Sun, Hong-Zhi (Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University) ;
- Zhu, Shi-Tu (Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University) ;
- Lu, Hang (Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University) ;
- Niu, Zhe-Feng (Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University) ;
- Guo, Wen-Feng (Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University) ;
- Takano, Yasuo (Clinical Research Institute, Kanagawa Cancer Center) ;
- Zheng, Hua-Chuan (Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University)
- Published : 2013.07.30
Background: Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells. Methods: DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays. Results: The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78,
Colon carcinoma cells;parafibromin;cell phenotypes;molecular mechanisms
Supported by : Natural Scientific Foundation of China
- Aldred MJ, Talacko AA, Savarirayan R, et al (2006). Dental findings in a family with hyperparathyroidism- jaw tumour syndrome and a novel HRPT2 gene mutation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 101, 212-8. https://doi.org/10.1016/j.tripleo.2005.06.011
- Cui C, Lal P, Master S, et al (2012). Expression of parafibromin in major renal cell tumors. Eur J Histochem, 56, e39. https://doi.org/10.4081/ejh.2012.e39
- Gill AJ, Clarkson A, Gimm O, et al (2006). Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism- jaw tumour (HPTJT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol, 30, 1140-9.
- Hahn MA, Dickson KA, Jackson S, et al (2011). The tumor suppressor CDC73 interacts with the ring finger proteins RNF20 and RNF40 and is required for the maintenance of histone 2B monoubiquitination. Hum Mol Genet, 21, 559-68.
- Howell VM, Haven CJ, Kahnoski K, et al (2003). HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet, 40, 657-63. https://doi.org/10.1136/jmg.40.9.657
- Kambhampati S, Banerjee S, Dhar K, et al (2010). 2-methoxyestradiol inhibits Barrett's esophageal adenocarcinoma growth and differentiation through differential regulation of the beta-catenin-E-cadherin axis. Mol Cancer Ther, 9, 523-34. https://doi.org/10.1158/1535-7163.MCT-09-0845
- Kumada T, Tsuneyama K, Hatta H, Ishizawa S, Takano Y (2004). Improved 1-h rapid immunostaining method using intermittent microwave irradiation: practicability based on 5 years application in Toyama Medical and Pharmaceutical University Hospital. Mod Pathol, 17, 1141-9. https://doi.org/10.1038/modpathol.3800165
- Lin L, Zhang JH, Panicker LM, Simonds WF (2008). The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene. Proc Natl Acad Sci U S A, 105, 17420-5. https://doi.org/10.1073/pnas.0710725105
- Newey PJ, Bowl MR, Thakker RV (2009). Parafibrominfunctional insights. J Intern Med, B, 84-98.
- O'Neill E, Kolch W (2004). Conferring specificity on the ubiquitous Raf/MEK signalling pathway. Br J Cancer, 90, 283-8. https://doi.org/10.1038/sj.bjc.6601488
- Owens P, Han G, Li AG, Wang XJ (2008). The role of Smads in skin development. J Invest Dermatol, 128, 783-90. https://doi.org/10.1038/sj.jid.5700969
- Sellins KS, Cohen JJ (1987). Gene induction by gammairradiation leads to DNA fragmentation in lymphocytes. J Immunol, 139, 3199-206.
- Selvarajan S, Sii LH, Lee A, et al (2008). Parafibromin expression in breast cancer: a novel marker for prognostication? J Clin Pathol, 61, 64-7.
- Shattuck TM, Välimäki S, Obara T, et al (2003). Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med, 349, 1722-9. https://doi.org/10.1056/NEJMoa031237
- Takahashi A, Tsutsumi R, Kikuchi I, et al (2011).SHP2 tyrosine phosphatase converts parafibromin/Cdc73 from a tumor suppressor to an oncogenic driver. Mol Cell, 43, 45-56. https://doi.org/10.1016/j.molcel.2011.05.014
- Tan MH, Wong CF, Tan HL, et al (2010).Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma. BMC Cancer, 10, 196. https://doi.org/10.1186/1471-2407-10-196
- Xia P, Wang W, Xu XY, et al (2011). Parafibromin expression in lung normal tissue and carcinoma: its comparison with clinicopathological parameters of carcinoma. Histol Histopathol, 26, 1039-47.
- Xiao LJ, Zhao S, Zhao GH, et al (2013). The clinicopathological and prognostic significance of ki-67, Caspase-3 and p53 expression in gastric carcinomas. Oncol Lett in press.
- Yamaguchi M (2013). The anti-apoptotic effect of regucalcin is mediated through multisignaling pathways. Apoptosis in press.
- Yang YJ, Han JW, Youn HD, Cho EJ (2010). The tumor suppressor, parafibromin, mediates histone H3 K9 methylation for cyclin D1 repression. Nucleic Acids Res, 38, 382-90. https://doi.org/10.1093/nar/gkp991
- Zhang C, Kong D, Tan MH, et al (2006). Parafibromin inhibits cancer cell growth and causes G1 phase arrest. Biochem Biophys Res Commun, 350, 17-24. https://doi.org/10.1016/j.bbrc.2006.08.169
- Zhao J, Yart A, Frigerio S, et al (2007). Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene. Oncogene, 26, 3440-9. https://doi.org/10.1038/sj.onc.1210131
- Zheng HC, Takahashi H, Li XH, et al (2008). Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas. Virchows Arch, 452, 147-55. https://doi.org/10.1007/s00428-007-0551-z
- Zheng HC, Takahashi H, Li XH, et al (2008). Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pathol, 39, 1042-9. https://doi.org/10.1016/j.humpath.2007.11.009
- Zheng HC, Wei ZL, Xu XY, et al (2011). Parafibromin expression is an independent prognostic factor for colorectal carcinomas. Hum Pathol, 42,1089-102. https://doi.org/10.1016/j.humpath.2010.10.024
- Zheng HC, Xu XY, Xia P, et al (2010). Involvement of inactive GSK3beta overexpression in tumorigenesis and progression of gastric carcinomas. Hum Pathol, 41, 1255-64. https://doi.org/10.1016/j.humpath.2010.02.003
- The clinicopathological significances and biological functions of parafibromin expression in head and neck squamous cell carcinomas vol.36, pp.12, 2015, https://doi.org/10.1007/s13277-015-3618-5
- The roles of parafibromin expression in ovarian epithelial carcinomas: a marker for differentiation and prognosis and a target for gene therapy vol.37, pp.3, 2016, https://doi.org/10.1007/s13277-015-4103-x